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Zhang RL, Wang WM, Li JQ, Li RW, Zhang J, Wu Y, Liu Y. The role of miR-155 in cardiovascular diseases: Potential diagnostic and therapeutic targets. INTERNATIONAL JOURNAL OF CARDIOLOGY. CARDIOVASCULAR RISK AND PREVENTION 2025; 24:200355. [PMID: 39760132 PMCID: PMC11699627 DOI: 10.1016/j.ijcrp.2024.200355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 11/21/2024] [Accepted: 12/05/2024] [Indexed: 01/07/2025]
Abstract
Cardiovascular diseases (CVDs), such as atherosclerotic cardiovascular diseases, heart failure (HF), and acute coronary syndrome, represent a significant threat to global health and impose considerable socioeconomic burdens. The intricate pathogenesis of CVD involves various regulatory mechanisms, among which microRNAs (miRNAs) have emerged as critical posttranscriptional regulators. In particular, miR-155 has demonstrated differential expression patterns across a spectrum of CVD and is implicated in the etiology and progression of arterial disorders. This systematic review synthesizes current evidence on the multifaceted roles of miR-155 in the modulation of genes and pathological processes associated with CVD. We delineate the potential of miR-155 as a diagnostic biomarker and therapeutic target, highlighting its significant regulatory influence on conditions such as atherosclerosis, aneurysm, hypertension, HF, myocardial hypertrophy, and oxidative stress. Our analysis underscores the transformative potential of miR-155 as a target for intervention in cardiovascular medicine, warranting further investigation into its clinical applicability.
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Affiliation(s)
- Rui-Lin Zhang
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Wei-Ming Wang
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital, Southwest Medical University, 646000, Luzhou, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Ji-Qiang Li
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Run-Wen Li
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jie Zhang
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Ya Wu
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital, Southwest Medical University, 646000, Luzhou, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Yong Liu
- Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital, Southwest Medical University, 646000, Luzhou, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China
- Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
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Santana E, Ibrahimi E, Ntalianis E, Cauwenberghs N, Kuznetsova T. Integrating Metabolomics Domain Knowledge with Explainable Machine Learning in Atherosclerotic Cardiovascular Disease Classification. Int J Mol Sci 2024; 25:12905. [PMID: 39684618 DOI: 10.3390/ijms252312905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/19/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Metabolomic data often present challenges due to high dimensionality, collinearity, and variability in metabolite concentrations. Machine learning (ML) application in metabolomic analyses is enabling the extraction of meaningful information from complex data. Bringing together domain-specific knowledge from metabolomics with explainable ML methods can refine the predictive performance and interpretability of models used in atherosclerosis research. In this work, we aimed to identify the most impactful metabolites associated with the presence of atherosclerotic cardiovascular disease (ASCVD) in cross-sectional case-control studies using explainable ML methods integrated with metabolomics domain knowledge. For this, a subset from the FLEMENGHO cohort with metabolomic data available was used as the training cohort, including 63 patients with a history of ASCVD and 52 non-smoking controls matched by age, sex, and body mass index from the same population. First, Partial Least Squares Discriminant Analysis (PLS-DA) was applied for dimensionality reduction. The selected metabolites' correlations were analyzed by considering their chemical categorization. Then, eXtreme Gradient Boosting (XGBoost) was used to identify metabolites that characterize ASCVD. Next, the selected metabolites were evaluated in an external cohort to determine their effectiveness in distinguishing between cases and controls. A total of 56 metabolites were selected for ASCVD discrimination using PLS-DA. The primary identified metabolites' superclasses included lipids, organic acids, and organic oxygen compounds. Upon integrating these metabolites with the XGBoost model, the classification yielded a test area under the curve (AUC) of 0.75. SHAP analyses ranked cholesterol, 3-methylhistidine, and glucuronic acid among the most impactful features and showed the diversity of metabolites considered for building the ASCVD discriminator. Also using XGBoost, the selected metabolites achieved an AUC of 0.93 in an independent external validation cohort. In conclusion, the combination of different metabolites has the potential to build classifiers for ASCVD. Integrating metabolite categorization within the SHAP analysis further enhanced the interpretability of the model, offering insights into metabolite-specific contributions to ASCVD risk.
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Affiliation(s)
- Everton Santana
- Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium
| | - Eliana Ibrahimi
- Department of Biology, University of Tirana, 1001 Tirana, Albania
| | - Evangelos Ntalianis
- Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium
| | - Nicholas Cauwenberghs
- Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium
| | - Tatiana Kuznetsova
- Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium
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Shao Y, Xu J, Chen W, Hao M, Liu X, Zhang R, Wang Y, Dong Y. miR-135b: An emerging player in cardio-cerebrovascular diseases. J Pharm Anal 2024; 14:100997. [PMID: 39211791 PMCID: PMC11350494 DOI: 10.1016/j.jpha.2024.100997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 04/20/2024] [Accepted: 05/03/2024] [Indexed: 09/04/2024] Open
Abstract
miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.
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Affiliation(s)
- Yingchun Shao
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Jiazhen Xu
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Wujun Chen
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Minglu Hao
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Xinlin Liu
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Renshuai Zhang
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Yanhong Wang
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
| | - Yinying Dong
- The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, China
- Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China
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Fux E, Lenski M, Bendt AK, Otvos JD, Ivanisevic J, De Bruyne S, Cavalier E, Friedecký D. A global perspective on the status of clinical metabolomics in laboratory medicine - a survey by the IFCC metabolomics working group. Clin Chem Lab Med 2024; 62:1950-1961. [PMID: 38915248 DOI: 10.1515/cclm-2024-0550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/15/2024] [Indexed: 06/26/2024]
Abstract
OBJECTIVES Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation. METHODS A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed. RESULTS Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology. CONCLUSIONS Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine.
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Affiliation(s)
- Elie Fux
- Roche Diagnostics GmbH, Penzberg, Germany
| | - Marie Lenski
- ULR 4483, IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, Univ. Lille, Institut Pasteur de Lille et Unité Fonctionnelle de Toxicologie, CHU Lille, Lille, France
| | - Anne K Bendt
- Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore
| | - James D Otvos
- Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Julijana Ivanisevic
- Metabolomics Unit, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Sander De Bruyne
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Etienne Cavalier
- Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium
| | - David Friedecký
- Department of Clinical Biochemistry, University Hospital Olomouc, Olomouc, Czechia
- Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic
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Lin H, Yao T, Ding H, Chu J, Yuan D, Ping F, Chen F, Liu X. Identification and functional characterization of differentially expressed circRNAs in high glucose treated endothelial cells: Construction of circRNA-miRNA-mRNA network. Heliyon 2024; 10:e37028. [PMID: 39281534 PMCID: PMC11399645 DOI: 10.1016/j.heliyon.2024.e37028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/31/2024] [Accepted: 08/26/2024] [Indexed: 09/18/2024] Open
Abstract
Background Endothelial dysfunction is a complication of diabetes mellitus (DM), characterized by impaired endothelial function in both microvessels and macrovessels, closely linked to atherosclerosis (AS). Endothelial dysfunction, characterized by impaired endothelial cell (EC) function, is a pivotal factor in AS and DM. Circular RNAs (circRNAs) are endogenous non-coding RNAs that can act as competing endogenous RNAs (ceRNAs) and regulate gene expression. However, the role of circRNAs in ECs dysfunction and AS under high glucose (HG) condition remains elusive. Methods We performed high-throughput sequencing to identify differentially expressed (DE) circRNAs in human umbilical vein endothelial cells (HUVEC) exposed to HG, one risk factors of endothelial dysfunction and AS. We then validated eight candidate circRNAs by qRT-PCR and functional analysis, directing our attention to hsa_circ_0122319. Moreover, microarray analysis identified the differential expression profiles of miRNAs and mRNAs regulated by hsa_circ_0122319. Subsequently, the construction of the ceRNAs network employed bioinformatic analysis and Cytoscape software. Furthermore, the role of the PI3K-Akt signaling pathway in regulating ceRNAs was evaluated. Results We detected 917 DE circRNAs in HG treated HUVEC. The parental genes of these circRNAs were enriched in cell cycle, cellular senescence and endocytosis related pathways. The differential expression of hsa_circ_0122319 was confirmed to be most obvious at the cellular level and in clinical samples by qPCR experiments. After overexpression of hsa_circ_0122319, 49 DE miRNAs and 459 DE mRNAs were identified using microarray analysis. Subsequently, a ceRNAs network was constructed, comprising hsa_circ_0122319, 8 miRNAs, and 41 mRNAs. Conclusion In summary, our study delves into the role of circRNAs in endothelial dysfunction associated with DM and AS. Through high-throughput sequencing and validation, we identified hsa_circ_0122319 as a pivotal regulator of ECs function under HG conditions. It also showed that hsa_circ_0123319 has the potential to serve as a biomarker for DM and its vascular complications, and provides new evidence for future exploration of the intricate molecular mechanisms of endothelial dysfunction in the progression of DM and AS.
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Affiliation(s)
- Hao Lin
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Tongqing Yao
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Haoran Ding
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Jiapeng Chu
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Deqiang Yuan
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Fan Ping
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Fei Chen
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
| | - Xuebo Liu
- Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, 200092, Shanghai, China
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Ao L, Noordam R, Rensen PCN, van Heemst D, Willems van Dijk K. The role of genetically-influenced phospholipid transfer protein activity in lipoprotein metabolism and coronary artery disease. J Clin Lipidol 2024; 18:e579-e587. [PMID: 38906750 DOI: 10.1016/j.jacl.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 02/20/2024] [Accepted: 03/26/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Phospholipid transfer protein (PLTP) transfers surface phospholipids between lipoproteins and as such plays a role in lipoprotein metabolism, but with unclear effects on coronary artery disease (CAD) risk. We aimed to investigate the associations of genetically-influenced PLTP activity with 1-H nuclear magnetic resonance (1H-NMR) metabolomic measures and with CAD. Furthermore, using factorial Mendelian randomization (MR), we examined the potential additional effect of genetically-influenced PLTP activity on CAD risk on top of genetically-influenced low-density lipoprotein-cholesterol (LDL-C) lowering. METHODS Using data from UK Biobank, genetic scores for PLTP activity and LDL-C were calculated and dichotomised based on the median, generating four groups with combinations of high/low PLTP activity and high/low LDL-C levels for the factorial MR. Linear and logistic regressions were performed on 168 metabolomic measures (N = 58,514) and CAD (N = 318,734, N-cases=37,552), respectively, with results expressed as β coefficients (in standard deviation units) or odds ratios (ORs) and 95% confidence interval (CI). RESULTS Irrespective of the genetically-influenced LDL-C, genetically-influenced low PLTP activity was associated with a higher high-density lipoprotein (HDL) particle concentration (β [95% CI]: 0.03 [0.01, 0.05]), smaller HDL size (-0.14 [-0.15, -0.12]) and higher triglyceride (TG) concentration (0.04 [0.02, 0.05]), but not with CAD (OR 0.99 [0.97, 1.02]). In factorial MR analyses, genetically-influenced low PLTP activity and genetically-influenced low LDL-C had independent associations with metabolomic measures, and genetically-influenced low PLTP activity did not show an additional effect on CAD risk. CONCLUSIONS Low PLTP activity associates with higher HDL particle concentration, smaller HDL particle size and higher TG concentration, but no association with CAD risk was observed.
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Affiliation(s)
- Linjun Ao
- Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands (MMed Ao and Dr Willems van Dijk).
| | - Raymond Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands (Drs Noordam and van Heemst)
| | - Patrick C N Rensen
- Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands (Drs Rensen and Willems van Dijk); Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands (Drs Rensen and Willems van Dijk)
| | - Diana van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands (Drs Noordam and van Heemst)
| | - Ko Willems van Dijk
- Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands (MMed Ao and Dr Willems van Dijk); Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands (Drs Rensen and Willems van Dijk); Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands (Drs Rensen and Willems van Dijk)
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Li H, Li L, Huang QQ, Yang SY, Zou JJ, Xiao F, Xiang Q, Liu X, Yu R. Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study. World J Diabetes 2024; 15:1021-1044. [PMID: 38766424 PMCID: PMC11099375 DOI: 10.4239/wjd.v15.i5.1021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 01/28/2024] [Accepted: 03/18/2024] [Indexed: 05/10/2024] Open
Abstract
BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries. AIM To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years. METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language. RESULTS A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years. CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.
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Affiliation(s)
- Hong Li
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Liu Li
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Qiu-Qing Huang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Si-Yao Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Jun-Ju Zou
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Fan Xiao
- College of International Education, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Qin Xiang
- Department of Science and Technology, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Xiu Liu
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Rong Yu
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
- College of Graduate, Hunan University of Chinese Medicine, Hunan Changsha, Hunan Province, China
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Zhong J, Chen H, Liu Q, Zhou S, Liu Z, Xiao Y. GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation. J Pharm Anal 2024; 14:100917. [PMID: 38799233 PMCID: PMC11127228 DOI: 10.1016/j.jpha.2023.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 10/15/2023] [Accepted: 12/07/2023] [Indexed: 05/29/2024] Open
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many medical conditions, including hypertension, diabetes, obesity, sleep apnea, and heart failure (HF), increase the risk for AF. Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production. Significant changes occur in myocardial metabolism in AF. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus (T2DM) and obesity. GLP-1RAs have also been shown to reduce oxidative stress, inflammation, autonomic nervous system modulation, and mitochondrial function. This article reviews the changes in metabolic characteristics in cardiomyocytes in AF. Although the clinical trial outcomes are unsatisfactory, the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors, lowering the incidence of AF.
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Affiliation(s)
- Jiani Zhong
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Xiangya School of Medicine, Central South University, Changsha, 410008, China
| | - Hang Chen
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Xiangya School of Medicine, Central South University, Changsha, 410008, China
| | - Qiming Liu
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Shenghua Zhou
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Zhenguo Liu
- Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Missouri, Columbia, MO, 65211, USA
| | - Yichao Xiao
- Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
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Febra C, Saraiva J, Vaz F, Macedo J, Al-Hroub HM, Semreen MH, Maio R, Gil V, Soares N, Penque D. Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study. J Transl Med 2024; 22:200. [PMID: 38402378 PMCID: PMC10894498 DOI: 10.1186/s12967-024-04883-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 01/10/2024] [Indexed: 02/26/2024] Open
Abstract
BACKGROUND Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. METHODS This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). CONCLUSIONS Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.
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Affiliation(s)
- Cláudia Febra
- Department of Intensive Care, Hospital da Luz Lisboa, Lisbon, Portugal.
- Faculty of Medicine, University of Porto, Porto, Portugal.
- Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
| | - Joana Saraiva
- Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal
- Center for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School-FCM, UNL, Lisbon, Portugal
- NOVA School of Science and Technology, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Fátima Vaz
- Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal
- Center for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School-FCM, UNL, Lisbon, Portugal
| | - João Macedo
- NOVA School of Science and Technology, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Hamza Mohammad Al-Hroub
- Department of Medical Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohammad Harb Semreen
- Department of Medical Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
| | - Rui Maio
- Department of General Surgery, Hospital da Luz Lisboa, Lisbon, Portugal
| | - Vitor Gil
- Faculty of Medicine, University of Porto, Porto, Portugal
- Center of Cardiovascular Risk and Thrombosis, Hospital da Luz Torres de Lisboa, Lisbon, Portugal
| | - Nelson Soares
- Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
- NOVA School of Science and Technology, Universidade Nova de Lisboa, Lisbon, Portugal.
- Department of Medical Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
| | - Deborah Penque
- Human Genetics Department, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
- Center for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School-FCM, UNL, Lisbon, Portugal.
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10
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Xu T, Jiang Y, Fu H, Yang G, Hu X, Chen Y, Zhang Q, Wang Y, Wang Y, Xie HQ, Han F, Xu L, Zhao B. Exploring the adverse effects of 1,3,6,8-tetrabromo-9H-carbazole in atherosclerotic model mice by metabolomic profiling integrated with mechanism studies in vitro. CHEMOSPHERE 2024; 349:140767. [PMID: 37992903 DOI: 10.1016/j.chemosphere.2023.140767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/04/2023] [Accepted: 11/17/2023] [Indexed: 11/24/2023]
Abstract
Given its wide distribution in the environment and latent toxic effects, 1,3,6,8-tetrabromo-9H-carbazole (1368-BCZ) is an emerging concern that has gained increasing attention globally. 1368-BCZ exposure is reported to have potential cardiovascular toxicity. Although atherosclerosis is a cardiovascular disease and remains a primary cause of mortality worldwide, no evidence has been found regarding the impact of 1368-BCZ on atherosclerosis. Therefore, we aimed to explore the deleterious effects of 1368-BCZ on atherosclerosis and the underlying mechanisms. Serum samples from 1368-BCZ-treated atherosclerotic model mice were subjected to metabolomic profiling to investigate the adverse influence of the pollutant. Subsequently, the molecular mechanism associated with the metabolic pathway of atherosclerotic mice that was identified following 1368-BCZ exposure was validated in vitro. Serum metabolomics analysis revealed that 1368-BCZ significantly altered the tricarboxylic acid cycle, causing a disturbance in energy metabolism. In vitro, we further validated general markers of energy metabolism based on metabolome data: 1368-BCZ dampened adenosine triphosphate (ATP) synthesis and increased reactive oxygen species (ROS) production. Furthermore, blocking the aryl hydrocarbon receptor (AhR) reversed the high production of ROS induced by 1368-BCZ. It is concluded that 1368-BCZ decreased the ATP synthesis by disturbing the energy metabolism, thereby stimulating the AhR-mediated ROS production and presumably causing aggravated atherosclerosis. This is the first comprehensive study on the cardiovascular toxicity and mechanism of 1368-BCZ based on rodent models of atherosclerosis and integrated with in vitro models.
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Affiliation(s)
- Tong Xu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China; PET/CT Center, Key Laboratory of Functional Molecular Imaging, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China
| | - Yu Jiang
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Hualing Fu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Guanglei Yang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiaoxu Hu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yangsheng Chen
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qian Zhang
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, 100730, China
| | - Yuxi Wang
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Yilan Wang
- PET/CT Center, Key Laboratory of Functional Molecular Imaging, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China
| | - Heidi Qunhui Xie
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Fang Han
- PET/CT Center, Key Laboratory of Functional Molecular Imaging, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
| | - Li Xu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Bin Zhao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China
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11
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Yan S, Liu G, Chen X. Spatiotemporal distribution characteristics and influencing factors of the rate of cardiovascular hospitalization in Ganzhou city of China. Front Cardiovasc Med 2023; 10:1225878. [PMID: 38188258 PMCID: PMC10770874 DOI: 10.3389/fcvm.2023.1225878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 12/04/2023] [Indexed: 01/09/2024] Open
Abstract
Aims The objective of this study was to analyze hospitalization rates for cardiovascular diseases (CVD) in Ganzhou City, Jiangxi Province of China from 2015 to 2020 and to uncover the spatiotemporal distribution characteristics and influencing factors, and thus to provide reference for the prevention and control of CVD and public health resources planning. Methods The hospitalization data for CVDs from 2016 to 2020 was obtained from the First Affiliated Hospital of Gannan Medical University, and ArcGIS 10.8, SaTScan 9.5, and Matlab 20.0 were used to analyze the spatial autocorrelation, spatiotemporal scan statistics, and potential affecting factors of the hospitalization rates. Results The hospitalization rate for CVDs in Ganzhou City showed a slightly increasing trend from 2016 to 2020, with higher rates in winter and summer than that in spring and autumn, and the individuals aged 61 and above constitute a higher proportion compared to other age groups. Additionally, there was a positive correlation between hospitalization rates for CVDs and the counties and districts in Ganzhou City, with high-high aggregation areas mainly distributed in Nankang District, the western urban area of Ganzhou City. The spatial scan analysis identified three different types of significant aggregation areas: high-risk, low-risk, and middle-risk areas. The high-risk area was mainly centered around Zhanggong District or Shangyu County in the central and western regions, with a disease hospitalization rate 2-3 times higher than the rest areas. The study also found that environmental meteorological factors such as the annual average concentration of NO2, O3, average annual temperature, and annual maximum temperature diurnal range had a significant positive effect on hospitalization rates for CVDs in Ganzhou City, with O3 concentration and average annual temperature having significant positive indirect spatial spillover effects. Conclusion Winter and summer are the seasons with high hospitalization rate of cardiovascular diseases. County residents aged 61 and above are the higher-risk population that needs to pay more attention on for prevention and control of CVD in Ganzhou City, which exhibits significant spatiotemporal clustering. The urban areas of Zhanggong and Nankang in Ganzhou City are the key areas for prevention and control of CVD. The hospitalization rate of CVD in Ganzhou City is influenced by the aforementioned four environmental meteorological factors, with the annual maximum temperature diurnal range showing the most significant positive direct effect.
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Affiliation(s)
- Shanshan Yan
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China
| | - Guoqiu Liu
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, China
| | - Xiaoyuan Chen
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, China
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12
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Sardar SW, Nam J, Kim TE, Kim H, Park YH. Identification of Novel Biomarkers for Early Diagnosis of Atherosclerosis Using High-Resolution Metabolomics. Metabolites 2023; 13:1160. [PMID: 37999255 PMCID: PMC10673153 DOI: 10.3390/metabo13111160] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/14/2023] [Accepted: 11/16/2023] [Indexed: 11/25/2023] Open
Abstract
Atherosclerosis (AS) is a metabolic disorder and the pre-stage of several cardiovascular diseases, including myocardial infarction, stroke, and angina pectoris. Early detection of AS can provide the opportunity for effective management and better clinical results, along with the prevention of further progression of the disease. In the current study, an untargeted and targeted metabolomic approach was used to identify possible metabolic signatures that have altered levels in AS patients. A total of 200 serum samples from individuals with AS and normal were analyzed via liquid chromatography-high-resolution mass spectrometry. Univariate and multivariate analysis approaches were used to identify differential metabolites. A group of metabolites associated with bile acids, amino acids, steroid hormones, and purine metabolism were identified that are capable of distinguishing AS-risk sera from normal. Further, the targeted metabolomics approach confirmed that six metabolites, namely taurocholic acid, cholic acid, cortisol, hypoxanthine, trimethylamine N-oxide (TMAO), and isoleucine, were found to be significantly upregulated, while the concentrations of glycoursodeoxycholic acid, glycocholic acid, testosterone, leucine, methionine, phenylalanine, tyrosine, and valine were found to be significantly downregulated in the AS-risk sera. The receiver operating characteristic curves of three metabolites, including cortisol, hypoxanthine, and isoleucine, showed high sensitivity and specificity. Taken together, these findings suggest cortisol, hypoxanthine, and isoleucine as novel biomarkers for the early and non-invasive detection of AS. Thus, this study provides new insights for further investigations into the prevention and management of AS.
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Affiliation(s)
- Syed Wasim Sardar
- Omics Research Center, Korea University, Sejong 30019, Republic of Korea; (S.W.S.); (T.E.K.); (H.K.)
| | - Jeonghun Nam
- Artificial Intelligence (AI)-Bio Research Center, Incheon Jaeneung University, Incheon 22573, Republic of Korea;
| | - Tae Eun Kim
- Omics Research Center, Korea University, Sejong 30019, Republic of Korea; (S.W.S.); (T.E.K.); (H.K.)
| | - Hyunil Kim
- Omics Research Center, Korea University, Sejong 30019, Republic of Korea; (S.W.S.); (T.E.K.); (H.K.)
| | - Youngja H. Park
- Omics Research Center, Korea University, Sejong 30019, Republic of Korea; (S.W.S.); (T.E.K.); (H.K.)
- Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong 30019, Republic of Korea
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13
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Shen L, Wang J, Pan Y, Huang J, Zhu K, Tu H, Chen M. Characteristics of Metabolites in the Development of Atherosclerosis in Tibetan Minipigs Determined Using Untargeted Metabolomics. Nutrients 2023; 15:4425. [PMID: 37892500 PMCID: PMC10609677 DOI: 10.3390/nu15204425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/14/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Atherosclerosis (AS) is a chronic progressive disease caused by lipometabolic disorder. However, the pathological characteristics and mechanism of AS have not been fully clarified. Through high-fat and high-cholesterol diet induction, Tibetan minipigs can be used as the AS model animals, as they have a very similar AS pathogenesis to humans. METHODS In this study, we built an AS model of Tibetan minipigs and identified the differential abundance metabolites in the development of AS based on untargeted metabolomics. RESULTS We found that sphingolipid metabolism and glucose oxidation were obviously higher in the AS group and phenylalanine metabolism was reduced in the AS group. Moreover, in the development of AS, gluconolactone was enriched in the late stage of AS whereas biopterin was enriched in the early stage of AS. CONCLUSIONS Our research provides novel clues to investigate the metabolic mechanism of AS from the perspective of metabolomics.
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Affiliation(s)
- Liye Shen
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
- Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China;
| | - Jinlong Wang
- Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310024, China;
| | - Yongming Pan
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
| | - Junjie Huang
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
| | - Keyan Zhu
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
| | - Haiye Tu
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
| | - Minli Chen
- Academy of Chinese Medicine & Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310024, China; (L.S.); (Y.P.); (J.H.); (K.Z.); (H.T.)
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14
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Du Z, Zhao X, Sun L, Chi B, Ma Z, Tian Z, Liu Y. Untargeted lipidomics-based study reveals the treatment mechanism of Qingxue Bawei tablets on atherosclerotic in ApoE -/- mice. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1229:123889. [PMID: 37738809 DOI: 10.1016/j.jchromb.2023.123889] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 09/24/2023]
Abstract
Qingxue Bawei (QXBW) tablets, a Mongolian medicine prescription, have proved to possess good lipid-lowering and antihypertensive effects in previous studies. However, the therapeutic effects and potential mechanisms of QXBW tablets on atherosclerosis (AS) have not been well studied yet. This study aimed to investigate the potential liver-protective mechanism of QXBW tablets on AS mice by hepatic lipidomics analysis. After 10 weeks of administration, serum and liver were collected for biochemical, histopathological, and lipid metabolomics analysis to evaluate the efficacy of the QXBW tablets on high-fat diet (HFD) induced mice. The experimental results indicated that QXBW tablets could ameliorate liver injury and inflammatory response in AS mice. Liver lipid data from different groups of mice were collected by UPLC-Q-Orbitrap-MS, and a total of 22 potential biomarkers with significant differences between the model and control groups were identified finally, of which 16 potential biomarkers were back-regulated after the QXBW tablets intervention. These 22 potential differential metabolic markers were mainly involved in glycerolipid metabolism, glycerophospholipid metabolism, and cholesterol ester metabolism pathways. The results of this study showed that serum inflammatory factors, liver function indices, and lipid metabolism disorders were positively alleviated in AS mice after QXBW tablets treatment.
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Affiliation(s)
- Zhen Du
- Innovation Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Xin Zhao
- Pharmacy Department of Boshan District Hospital, Zibo City, Shandong Province, Zibo 255000, China
| | - Luping Sun
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Bingqing Chi
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zhen Ma
- Innovation Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Zhenhua Tian
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| | - Yuecheng Liu
- Shandong Academy of Chinese Medicine, Jinan 250014, China.
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15
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Harshfield EL, Markus HS. Association of Baseline Metabolomic Profiles With Incident Stroke and Dementia and With Imaging Markers of Cerebral Small Vessel Disease. Neurology 2023; 101:e489-e501. [PMID: 37290969 PMCID: PMC10401678 DOI: 10.1212/wnl.0000000000207458] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 04/13/2023] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Cerebral small vessel disease is a major cause of stroke and dementia. Metabolomics can help identify novel risk factors to better understand pathogenesis and predict disease progression and severity. METHODS We analyzed baseline metabolomic profiles from 118,021 UK Biobank participants. We examined cross-sectional associations of 325 metabolites with MRI markers of small vessel disease, evaluated longitudinal associations with incident stroke and dementia, and ascertained causal relationships using Mendelian randomization. RESULTS In cross-sectional analyses, lower levels of apolipoproteins, free cholesterol, cholesteryl esters, fatty acids, lipoprotein particle concentrations, phospholipids, and triglycerides were associated with increased white matter microstructural damage on diffusion tensor MRI. In longitudinal analyses, lipoprotein subclasses of very large high-density lipoprotein cholesterol (HDL) were associated with an increased risk of stroke, and acetate and 3-hydroxybutyrate were associated with an increased risk of dementia. Mendelian randomization analyses identified strong evidence supporting causal relationships for many findings. A few metabolites had consistent associations across multiple analysis types. Increased total lipids in very large HDL and increased HDL particle size were associated with increased white matter damage (lower fractional anisotropy: OR: 1.44, 95% CI 1.07-1.95, and OR: 1.19, 95% CI 1.06-1.34, respectively; mean diffusivity: OR: 1.49, 95% CI 1.11-2.01, and OR: 1.24, 95% CI 1.11-1.40, respectively) and an increased risk of incident all stroke (HR: 4.04, 95% CI 2.13-7.64, and HR: 1.54, 95% CI 1.20-1.98, respectively) and ischemic stroke (HR: 3.12, 95% CI 1.53-6.38; HR: 1.37, 95% CI 1.04-1.81). Valine was associated with decreased mean diffusivity (OR: 0.51, 95% CI 0.30-0.88) and had a protective association with all-cause dementia (HR: 0.008, 95% CI 0.002-0.035). Increased levels of cholesterol in small HDL were associated with a decreased risk of incident all stroke (HR: 0.17, 95% CI 0.08-0.39) and ischemic stroke (HR: 0.19, 95% CI 0.08-0.46) and were supported by evidence of a causal association with MRI-confirmed lacunar stroke (OR: 0.96, 95% CI 0.93-0.99). DISCUSSION In this large-scale metabolomics study, we found multiple metabolites associated with stroke, dementia, and MRI markers of small vessel disease. Further studies may help inform the development of personalized prediction models and provide insights into mechanistic pathways and future treatment approaches.
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Affiliation(s)
- Eric L Harshfield
- From the Stroke Research Group (E.L.H., H.S.M.), Department of Clinical Neurosciences, University of Cambridge; and Victor Phillip Dahdaleh Heart and Lung Research Institute (E.L.H., H.S.M.), University of Cambridge, United Kingdom.
| | - Hugh S Markus
- From the Stroke Research Group (E.L.H., H.S.M.), Department of Clinical Neurosciences, University of Cambridge; and Victor Phillip Dahdaleh Heart and Lung Research Institute (E.L.H., H.S.M.), University of Cambridge, United Kingdom
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16
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Li Z, Zhu H, Liu H, Liu D, Liu J, Jiang J, Zhang Y, Qin Z, Xu Y, Peng Y, Liu B, Long Y. Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy. J Nanobiotechnology 2023; 21:158. [PMID: 37208681 DOI: 10.1186/s12951-023-01904-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/19/2023] [Indexed: 05/21/2023] Open
Abstract
PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.
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Affiliation(s)
- Zhenxian Li
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Haimei Zhu
- Department of Pain, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China
| | - Hao Liu
- Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Dayue Liu
- Department of Physiology and Pathophysiology, NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China
| | - Jianhe Liu
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Jiazheng Jiang
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Yi Zhang
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Zhang Qin
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Yijia Xu
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Yuan Peng
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China
| | - Bin Liu
- College of Biology, Hunan University, Changsha, 410082, China.
- Department of Physiology and Pathophysiology, NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
| | - Yun Long
- Department of Cardiology, The First Hospital of Hunan University of Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, 410007, China.
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Jiang X, Ma C, Gao Y, Cui H, Zheng Y, Li J, Zong W, Zhang Q. Tongxinluo attenuates atherosclerosis by inhibiting ROS/NLRP3/caspase-1-mediated endothelial cell pyroptosis. JOURNAL OF ETHNOPHARMACOLOGY 2023; 304:116011. [PMID: 36529253 DOI: 10.1016/j.jep.2022.116011] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/30/2022] [Accepted: 12/01/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tongxinluo (TXL) is one of the most common traditional Chinese medicines and plays a vital role in treating atherosclerosis (AS). Endothelial cell (EC) pyroptosis plays a crucial role in the development of AS. Previous research revealed the inhibitory function of TXL in EC apoptosis and autophagy. However, whether TXL can inhibit the pyroptosis of ECs has not been determined. AIM OF THE STUDY To explore the influence of TXL on EC pyroptosis and determine its underlying mechanism of action in AS. MATERIALS AND METHODS The TXL components were determined by ultra-performance liquid chromatography coupled with a photodiode array detector. We used ApoE-/- mice to establish a disease model of AS. After treatment with TXL, we recorded pathological changes in the mice and performed immunofluorescence staining of mice aortas. We also measured protein and gene levels to explore the influence of TXL on pyroptosis in vivo. The model was established by stimulating mouse aortic endothelial cells (MAECs) with oxidized low-density lipoprotein (ox-LDL) and analyzing the effect of TXL on pyroptosis by Western blotting (WB), real-time PCR (RT-PCR), and flow cytometry (FCM). We also investigated the impact of TXL on reactive oxygen species (ROS) by FCM and WB. RESULTS Ten major components of TXL were detected. The vivo results showed that TXL inhibited the development of AS and decreased EC pyroptosis, the activation of caspase-1, and the release of inflammatory cytokines. The vitro experiments showed that TXL significantly reduced the extent of injury to MAECs by oxidized LDL (ox-LDL). TXL reversed the high expression of gasdermin D and other proteins induced by ox-LDL and had a significant synergistic effect with the caspase-1 inhibitor VX-765. We also confirmed that TXL decreased the accumulation of ROS and the expression levels of its essential regulatory proteins Cox2 and iNOS. When ROS accumulation was reduced, EC pyroptotic damage was reduced accordingly. CONCLUSION Our results indicated that TXL inhibited EC pyroptosis in AS. Reducing the accumulation of ROS may be the essential mechanism of AS inhibition by TXL.
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Affiliation(s)
- Xuejiao Jiang
- Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Chongyang Ma
- Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Yanbin Gao
- Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Hehe Cui
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'An Road, Xicheng District, Beijing, 100050, PR China
| | - Yalin Zheng
- Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - JinXia Li
- Hunan University of Traditional Chinese Medicine, 113# Xueshi Road, Yuelu District, Changsha, Hunan, 410208, PR China
| | - Wenjing Zong
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 South Street, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China.
| | - Qiuyun Zhang
- Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
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18
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Fine KS, Wilkins JT, Sawicki KT. Clinical Metabolomic Landscape of Cardiovascular Physiology and Disease. J Am Heart Assoc 2023; 12:e027725. [PMID: 36892040 PMCID: PMC10111533 DOI: 10.1161/jaha.122.027725] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023]
Affiliation(s)
- Keenan S Fine
- Feinberg School of Medicine Northwestern University Chicago IL USA
| | - John T Wilkins
- Department of Preventive Medicine, Feinberg School of Medicine Northwestern University Chicago IL USA
- Division of Cardiology, Department of Medicine, Feinberg School of Medicine Northwestern University Chicago IL USA
| | - Konrad Teodor Sawicki
- Department of Preventive Medicine, Feinberg School of Medicine Northwestern University Chicago IL USA
- Division of Cardiology, Department of Medicine, Feinberg School of Medicine Northwestern University Chicago IL USA
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Wu Y, Zhao M, Gong N, Zhang F, Chen W, Liu Y. Immunometabolomics provides a new perspective for studying systemic lupus erythematosus. Int Immunopharmacol 2023; 118:109946. [PMID: 36931174 DOI: 10.1016/j.intimp.2023.109946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/20/2023] [Accepted: 02/23/2023] [Indexed: 03/18/2023]
Abstract
Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by clinical heterogeneity, unpredictable progression, and flare ups. Due to the heterogeneous nature of lupus, it has been challenging to identify sensitive and specific biomarkers for its diagnosis and monitoring. Despite the fact that the mechanism of SLE remains unknown, impressive progress has been made over the last decade towards understanding how different immune cells contribute to its pathogenesis. Research suggests that cellular metabolic programs could affect the immune response by regulating the activation, proliferation, and differentiation of innate and adaptive immune cells. Many studies have shown that the dysregulation of the immune system is associated with changes to metabolite profiles. The study of metabolite profiling may provide a means for mechanism exploration and novel biomarker discovery for disease diagnostic, classification, and monitoring. Here we review the latest advancements in understanding the role of immunometabolism in SLE, as well as the systemic metabolite profiling of this disease along with possible clinical application.
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Affiliation(s)
- Yuxian Wu
- College of Basic Medicine, Naval Medical University, Shanghai, China
| | - Mengpei Zhao
- Department of Pharmacy, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Na Gong
- College of Basic Medicine, Naval Medical University, Shanghai, China
| | - Feng Zhang
- Department of Pharmacy, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Wansheng Chen
- Department of Pharmacy, Changzheng Hospital, Naval Medical University, Shanghai, China.
| | - Yaoyang Liu
- Department of Rheumatology and Immunology, Changzheng Hospital, Naval Medical University, Shanghai, China.
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20
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Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study. Sci Rep 2023; 13:3296. [PMID: 36841863 PMCID: PMC9968318 DOI: 10.1038/s41598-023-30231-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 02/20/2023] [Indexed: 02/27/2023] Open
Abstract
Metabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.
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Nakamura E, Maekawa K, Saito Y, Matsumoto T, Ogawa M, Komohara Y, Asada Y, Yamashita A. Altered choline level in atherosclerotic lesions: Upregulation of choline transporter-like protein 1 in human coronary unstable plaque. PLoS One 2023; 18:e0281730. [PMID: 36800352 PMCID: PMC9937458 DOI: 10.1371/journal.pone.0281730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 01/30/2023] [Indexed: 02/18/2023] Open
Abstract
Inflammatory activity and hypoxia in atherosclerotic plaques are associated with plaque instability and thrombotic complications. Recent studies show that vascular cell metabolism affects atherogenesis and thrombogenicity. This study aimed to identify the metabolites in macrophage-rich unstable plaques that modulate atherogenesis and serve as potential markers of plaque instability. Atherosclerotic plaques were induced by balloon injury in the iliofemoral arteries of rabbits fed on a conventional or 0.5% cholesterol diet. At 3 months post-balloon injury, the arteries and cardiac tissues were subjected to histological, quantitative real-time polymerase chain reaction, and metabolomic analyses. The identified metabolite-related proteins were immunohistochemically analyzed in stable and unstable plaques from human coronary arteries. The factors modulating the identified metabolites were examined in macrophages derived from human peripheral blood mononuclear cells. Metabolomic analysis revealed that choline and guanine levels in macrophage-rich arteries were upregulated compared with those in non-injured arteries and cardiac tissues. Vascular choline levels, but not guanine levels, were positively correlated with the areas immunopositive for macrophages and tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP) 9 mRNA levels in injured arteries. In human coronary arteries, choline transporter-like protein (CTL) 1 was mainly localized to macrophages within plaques. The area that was immunopositive for CTL1 in unstable plaques was significantly higher than that in stable plaques. Intracellular choline levels were upregulated upon stimulation with TNF-α but were downregulated under hypoxia in cultured macrophages. Administration of choline upregulated the expression of TNF-α and CTL1 mRNA in cultured macrophages. The transfection of CTL1 small interfering RNA decreased CTL1, TNF-α, and MMP9 mRNA levels in cultured macrophages. These results suggest that choline metabolism is altered in macrophage-rich atherosclerotic lesions and unstable plaques. Thus, CTL1 may be potential markers of plaque instability.
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Affiliation(s)
- Eriko Nakamura
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kazunari Maekawa
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Yoichi Saito
- Bioengineering Lab, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan
| | - Tomoko Matsumoto
- Center for Collaborative Research and Community Cooperation, University of Miyazaki, Miyazaki, Japan
| | - Mikako Ogawa
- Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Science, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Yoshihiro Komohara
- Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yujiro Asada
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
- Department of Pathology, Miyazaki Medical Association Hospital, Miyazaki, Japan
| | - Atsushi Yamashita
- Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
- * E-mail:
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22
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Hetman M, Mielko K, Placzkowska S, Bodetko A, Młynarz P, Barg E. Predisposition to atherosclerosis in children and adults with trisomy 21: biochemical and metabolomic studies. Pediatr Endocrinol Diabetes Metab 2023; 29:143-155. [PMID: 38031830 PMCID: PMC10679913 DOI: 10.5114/pedm.2023.131162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 09/10/2023] [Indexed: 12/01/2023]
Abstract
INTRODUCTION Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population remain less explored. Aim of the study: This study examines the lipid profiles of DS in comparison to their siblings (CG), aiming to uncover potential atherosclerotic and CVD risks. MATERIAL AND METHODS The study included 42 people with DS (mean age 14.17 years) and the CG - 20 individuals (mean age 15.92 years). Anthropometric measurements: BMI, BMI SDS, and TMI were calculated. Lipid profile (LP) and metabolomics were determined. RESULTS LP: DS display significantly reduced HDL (DS vs. CG: 47±10 vs. 59 ±12 mg/dl; p = 0.0001) and elevated LDL (104 ±25 vs. 90 ±22 mg/dl; p = 0.0331). Triglycerides, APO A1, and APO B/APO A1 ratio corroborate with the elevated risk of CVD in DS. Despite no marked differences in: TCH and APO B, the DS group demonstrated a concerning BMI trend. Of 31 identified metabolites, 12 showed statistical significance (acetate, choline, creatinine, formate, glutamine, histidine, lysine, proline, pyroglutamate, threonine, tyrosine, and xanthine). However, only 8 metabolites passed the FDR validation (acetate, creatinine, formate, glutamine, lysine, proline, pyroglutamate, xanthine). CONCLUSIONS Down syndrome individuals show distinct cardiovascular risks, with decreased HDL and increased LDL levels. Combined with metabolomic disparities and higher BMI and TMI, this suggests an increased atherosclerosis risk compared to controls.
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Affiliation(s)
- Marta Hetman
- Department of Basic Medical Sciences, Wroclaw Medical University, Poland
| | - Karolina Mielko
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Poland
| | - Sylwia Placzkowska
- Teaching and Research Diagnostic Laboratory, Department of Laboratory Diagnostics, Wroclaw Medical University, Poland
| | - Aleksandra Bodetko
- Department of Basic Medical Sciences, Wroclaw Medical University, Poland
| | - Piotr Młynarz
- Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Poland
| | - Ewa Barg
- Department of Basic Medical Sciences, Wroclaw Medical University, Poland
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Li Q, Chen W, Huang W, Hou R, Huang X, Xu M, Que L, Wang L, Yang Y. 1H-NMR-Based Metabonomics Study to Reveal the Progressive Metabolism Regulation of SAP Deficiency on ApoE -/- Mice. Metabolites 2022; 12:metabo12121278. [PMID: 36557316 PMCID: PMC9785365 DOI: 10.3390/metabo12121278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/12/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Atherosclerosis is the most common disease of the vascular system and the metabolic disorder is one of its important molecular mechanisms. SAP protein is found to be highly expressed in atherosclerotic blood vessels. Our previous study found that SAP deficiency can significantly inhibit the development of atherosclerosis. However, the regulatory effect of SAP deficiency on AS metabolism is unknown. Based on 1H-NMR metabonomics, this study investigated the serum metabolic changes in ApoE-/-;SAP-/- mice compared with ApoE-/- mice during the whole progression of atherosclerosis. The results showed that acetate, pyruvate, choline and VLDL + LDL were statistically regulated to the normal levels as in C57 mice by SAP deficiency in ApoE-/-;SAP-/- mice at 8 w (without obvious plaques). With the appearance and aggravation of atherosclerotic plaques (8 + 4 w and 8 + 8 w), the four metabolites of acetate, pyruvate, choline and VLDL + LDL were continuously regulated, which were denoted as the metabolic regulatory markers of SAP deficiency. We also found that the changes in these four metabolites had nothing to do with high-fat diet. Therefore, it was revealed that SAP deficiency regulated the metabolic disorders in ApoE-/- prior to the appearance of obvious atherosclerotic plaques, which is one of the important mechanisms leading to the inhibition of atherosclerosis, providing a new basis for the application of SAP in atherosclerosis.
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Affiliation(s)
- Qian Li
- School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Wanting Chen
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Wenbin Huang
- Department of Breast Care Surgery, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Ranran Hou
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Xinping Huang
- School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Man Xu
- School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Limei Que
- Foshan Fosun Chancheng Hospital, Foshan 528031, China
| | - Lijing Wang
- School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yongxia Yang
- School of Medical Information and Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangzhou 510006, China
- Correspondence: ; Tel.: +86-(0)20-3935-2197
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24
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Galal A, Talal M, Moustafa A. Applications of machine learning in metabolomics: Disease modeling and classification. Front Genet 2022; 13:1017340. [PMID: 36506316 PMCID: PMC9730048 DOI: 10.3389/fgene.2022.1017340] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/07/2022] [Indexed: 11/25/2022] Open
Abstract
Metabolomics research has recently gained popularity because it enables the study of biological traits at the biochemical level and, as a result, can directly reveal what occurs in a cell or a tissue based on health or disease status, complementing other omics such as genomics and transcriptomics. Like other high-throughput biological experiments, metabolomics produces vast volumes of complex data. The application of machine learning (ML) to analyze data, recognize patterns, and build models is expanding across multiple fields. In the same way, ML methods are utilized for the classification, regression, or clustering of highly complex metabolomic data. This review discusses how disease modeling and diagnosis can be enhanced via deep and comprehensive metabolomic profiling using ML. We discuss the general layout of a metabolic workflow and the fundamental ML techniques used to analyze metabolomic data, including support vector machines (SVM), decision trees, random forests (RF), neural networks (NN), and deep learning (DL). Finally, we present the advantages and disadvantages of various ML methods and provide suggestions for different metabolic data analysis scenarios.
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Affiliation(s)
- Aya Galal
- Systems Genomics Laboratory, American University in Cairo, New Cairo, Egypt,Institute of Global Health and Human Ecology, American University in Cairo, New Cairo, Egypt
| | - Marwa Talal
- Systems Genomics Laboratory, American University in Cairo, New Cairo, Egypt,Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt
| | - Ahmed Moustafa
- Systems Genomics Laboratory, American University in Cairo, New Cairo, Egypt,Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt,Department of Biology, American University in Cairo, New Cairo, Egypt,*Correspondence: Ahmed Moustafa,
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25
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KONG XL, LYU Q, ZHANG YQ, KANG DF, LI C, ZHANG L, GAO ZC, LIU XX, WU JB, LI YL. Effect of astragaloside IV and salvianolic acid B on antioxidant stress and vascular endothelial protection in the treatment of atherosclerosis based on metabonomics. Chin J Nat Med 2022; 20:601-613. [DOI: 10.1016/s1875-5364(22)60186-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Indexed: 11/26/2022]
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Harshfield EL, Sands CJ, Tuladhar AM, de Leeuw FE, Lewis MR, Markus HS. Metabolomic profiling in small vessel disease identifies multiple associations with disease severity. Brain 2022; 145:2461-2471. [PMID: 35254405 PMCID: PMC9337813 DOI: 10.1093/brain/awac041] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 12/20/2021] [Accepted: 01/11/2022] [Indexed: 11/17/2022] Open
Abstract
Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity. We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54 764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition and future risk of all-cause dementia. Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensity volume, lower mean diffusivity normalized peak height, greater brain atrophy and impaired cognition. Higher levels of creatine, FA(18:2(OH)) and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensity volume and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualized change in peak width of skeletonized mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids and xenobiotics, were associated with future dementia incidence. Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.
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Affiliation(s)
- Eric L Harshfield
- Correspondence to: Dr Eric L. Harshfield Stroke Research Group Department of Clinical Neurosciences University of Cambridge R3, Box 83, Cambridge Biomedical Campus Cambridge CB2 0QQ, UK E-mail:
| | - Caroline J Sands
- National Phenome Centre, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK
| | - Anil M Tuladhar
- Department of Neurology, Donders Center for Medical Neuroscience, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands
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Prevalence and risk factors for vascular calcification based on the ankle-brachial index in the general population: a cross-sectional study. BMC Cardiovasc Disord 2022; 22:227. [PMID: 35585487 PMCID: PMC9118712 DOI: 10.1186/s12872-022-02668-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/06/2022] [Indexed: 11/13/2022] Open
Abstract
Background To investigate the prevalence of vascular calcification based on the ankle‐brachial index (ABI) value and analyse the risk factors for vascular calcification in the general population. Methods A cross-sectional study was conducted to collect clinical, laboratory, and lifestyle data in individuals aged 30–70 recruited from the physical examination centre. The automatic arteriosclerosis detector was used to measure the ABI. Difference tests, correlation analyses, and multivariate logistic regression analyses were performed to identify risk factors for vascular calcification. Results The overall prevalence of vascular calcification was 24.39% in 1033 subjects. The prevalence of vascular calcification in males was much higher than that in females (27.80% vs. 17.49%, P < 0.001). The differences in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), hypertension, and fatty liver disease were statistically significant in males (P < 0.05). The differences between serum uric acid (UA), total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), alcohol consumption, exercise, and postmenopausal status were statistically significant in females (P < 0.05). Increased age (odds ratio (OR) = 1.028, 95% confidence interval (CI) 1.008–1.049, P = 0.007), increased BMI (OR = 1.238, 95% CI 1.147–1.337, P < 0.001) and elevated DBP (OR = 2.563, 95% CI 1.262–5.205, P = 0.009) were independent risk factors for vascular calcification in males after adjusting for confounding factors. Increased BMI (OR = 1.159, 95% CI 1.029–1.304, P = 0.015), elevated UA (OR = 1.545, 95% CI 1.077–2.216, P = 0.018), elevated LDL-C (OR = 1.044, 95% CI 1.060–1.027, P < 0.001), and a lack of exercise (OR = 2.402, 95% CI 1.073–5.373, P = 0.033) were independent risk factors for vascular calcification in females. Conclusions The prevalence of vascular calcification based on the ABI value is also high in the general population of our centre. Increased age, BMI, and elevated DBP are independent risk factors for vascular calcification in males. Increased BMI, UA, LDL-C, and a lack of exercise are independent risk factors for vascular calcification in females. Attention should be given to strengthening the prevention and control of vascular calcification in the general population.
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Li Y, Cui W, Song B, Ye X, Li Z, Lu C. Autophagy-Sirtuin1(SIRT1) Alleviated the Coronary Atherosclerosis (AS)in Mice through Regulating the Proliferation and Migration of Endothelial Progenitor Cells (EPCs) via wnt/β-catenin/GSK3β Signaling Pathway. J Nutr Health Aging 2022; 26:297-306. [PMID: 35297474 DOI: 10.1007/s12603-022-1750-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND AND PURPOSE SIRT1 was associated with AS risk and EPCs were reported to participate in the endothelial repair in Coronary Atherosclerosis (CAS). In this study, we explored the role of SIRT1 in AS mice and also its modulation in EPCs. METHODS AND MATERIALS ApoE-/-mice were fed on high-fat and high-glucose diet to establish the AS animal model with the normally-raised C57BL/6 mice as a control group. SIRT1 activator, SRT 2104 was injected intravenously into 5 ApoE-/-mice and its inhibitor Nicotinamide was injected in tail in another 5 ApoE-/-mice. Weight changes were recorded. Blood samples were taken from posterior orbital venous plexus and were detected by automatic biochemical analyzer. HE staining displayed the pathological conditions while Immunohistochemistry (IHC) evaluated the CD34+/VEGFR2+ relative density in the aorta tissues. EPCs were isolated from bone marrow and verified using immunofluorescence staining (IFS). The modulatory mechanism of SIRT1 in EPCs were studied by using RT-PCR, MTT, Western Blot and colony formation, scratch methods. RESULTS SIRT1 activator negatively regulated the weight and TC, TG and LDL levels, alleviated the lesion conditions and decreased the CD34+/VEGFR2+ density compared to the AS control. In vitro, SIRT1 activator promoted the proliferation and migration of EPCs and activated wnt/β-catenin/GSK3β signaling pathway. SIRT1 activator also inhibited the autophagy biomarkers ATG1 and LC3II. Furthermore, inhibitor of autophagy promoted SIRT1 expression and induced EPC proliferation, migration and activated wnt/β-catenin/GSK3β pathway. The suppression of the wnt/β-catenin/GSK3β pathway inhibited SIRT1 expression in EPCs, attenuated the proliferation and migration and promoted autophagy of EPCs. CONCLUSION SIRT1 activation might be protective in AS mice through autophagy inhibition in EPCs via wnt/β-catenin/GSK3β signaling pathway.
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Affiliation(s)
- Y Li
- Chengzhi Lu, Department of Cardiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, Tianjin, 300110, China, ,
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Prediction model for different progressions of Atherosclerosis in ApoE-/- mice based on lipidomics. J Pharm Biomed Anal 2022; 214:114734. [DOI: 10.1016/j.jpba.2022.114734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 03/06/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023]
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30
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Maternal and Fetal Metabolites in Gestational Diabetes Mellitus: A Narrative Review. Metabolites 2022; 12:metabo12050383. [PMID: 35629887 PMCID: PMC9143359 DOI: 10.3390/metabo12050383] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/11/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is a major public health issue of our century due to its increasing prevalence, affecting 5% to 20% of all pregnancies. The pathogenesis of GDM has not been completely elucidated to date. Increasing evidence suggests the association of environmental factors with genetic and epigenetic factors in the development of GDM. So far, several metabolomics studies have investigated metabolic disruptions associated with GDM. The aim of this review is to highlight the usefulness of maternal metabolites as diagnosis markers of GDM as well as the importance of both maternal and fetal metabolites as prognosis biomarkers for GDM and GDM’s transition to type 2 diabetes mellitus T2DM.
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31
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Yu N, Wang R, Liu B, Zhang L. Bibliometric and Visual Analysis on Metabolomics in Coronary Artery Disease Research. Front Cardiovasc Med 2022; 9:804463. [PMID: 35402548 PMCID: PMC8990927 DOI: 10.3389/fcvm.2022.804463] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 02/28/2022] [Indexed: 12/13/2022] Open
Abstract
Background Metabolomics has immense research value in coronary artery disease and has drawn increasing attention over the past decades. Many articles have been published in this field, which may challenge researchers aiming to investigate all the available information. However, bibliometrics can provide deep insights into this research field. Objective We aimed to qualitatively and quantitatively study metabolomics and coronary artery disease research, visually analyse the development status, trends, research hotspots, and frontiers of this field, and provide a reference for research on coronary artery disease. Methods Articles were acquired from the Web of Science Core Collection. VOSviewer and CiteSpace software were used to analyse publication growth, country/region, institution, journal distribution, author, reference, and keywords, and detected the keywords with strong citation burstness to identify emerging topics. Results A total of 1121 references were obtained, and the annual number of publications increased over the past 16 years. Metabolomics research has shown a gradual upward trend in coronary artery disease. The United States of America and China ranked at the top in terms of percentage of articles. The institution with the highest number of research publications in this field was Harvard University, followed by the University of California System and Brigham Women's Hospital. The most frequently cited authors included Hazen SL, Tang WH, and Wang ZN. Ala-Korpela M was the most productive author, followed by Clish CB and Adamski J. The journal with the most publications in this field was Scientific Reports, followed by PLoS One and the Journal of Proteome Research. The keywords used at a high frequency were "risk," "biomarkers," "insulin resistance," and "atherosclerosis." Burst detection analysis of top keywords showed that "microbiota," "tryptophan," and "diabetes" are the current research frontiers in this field. Conclusion This study provides useful information for acquiring knowledge on metabolomics and coronary artery diseases. Metabolomics research has shown a gradual upward trend in coronary artery disease studies over the past 16 years. Research on tryptophan metabolism regulated by intestinal flora will become an emerging academic trend in this field, which can offer guidance for more extensive and in-depth studies in the future.
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Affiliation(s)
- Ning Yu
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ruirui Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Baocheng Liu
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lei Zhang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Yan Z, Zhang K, Zhang K, Wang G, Wang L, Zhang J, Qiu Z, Guo Z, Song X, Li J. Integrated 16S rDNA Gene Sequencing and Untargeted Metabolomics Analyses to Investigate the Gut Microbial Composition and Plasma Metabolic Phenotype in Calves With Dampness-Heat Diarrhea. Front Vet Sci 2022; 9:703051. [PMID: 35242833 PMCID: PMC8885629 DOI: 10.3389/fvets.2022.703051] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 01/10/2022] [Indexed: 12/26/2022] Open
Abstract
Dampness-heat diarrhea (DHD), a common syndrome in Chinese dairy farms, is mainly resulted from digestive system disorders, and accompanied with metabolic disorders in some cases. However, the underlying mechanisms in the intestinal microbiome and plasma metabolome in calves with DHD remain unclear. In order to investigate the pathogenesis of DHD in calves, multi-omics techniques including the 16S rDNA gene sequencing and metabolomics were used to analyze gut microbial compositions and plasma metabolic changes in calves. The results indicated that DHD had a significant effect on the intestinal microbial compositions in calves, which was confirmed by changes in microbial population and distribution. A total of 14 genera were changed, including Escherichia-Shigella, Bacteroides, and Fournierella, in calves with DHD (P < 0.05). Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that 11 metabolic functions (level 2) were significantly enriched in DHD cases. The untargeted metabolomics analysis showed that 440 metabolites including bilineurin, phosphatidylcholine, and glutamate were significantly different between two groups (VIP > 1 and P < 0.05), and they were related to 67 signal pathways. Eight signal pathways including alpha-linolenic acid, linoleic acid, and glycerophospholipid metabolism were significantly enriched (P < 0.05), which may be potential biomarkers of plasma in calves with DHD. Further, 107 pairs of intestinal microbiota-plasma metabolite correlations were determined, e.g., Escherichia-Shigella was significantly associated with changes of sulfamethazine, butyrylcarnitine, and 14 other metabolites, which reflected that metabolic activity was influenced by the microbiome. These microbiota-metabolite pairs might have a relationship with DHD in calves. In conclusion, the findings revealed that DHD had effect on intestinal microbial compositions and plasma metabolome in calves, and the altered metabolic pathways and microorganisms might serve as diagnostic markers and potential therapeutic targets for DHD in calves.
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Affiliation(s)
- Zunxiang Yan
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Kang Zhang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Kai Zhang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Guibo Wang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Lei Wang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Jingyan Zhang
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Zhengying Qiu
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Zhiting Guo
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
| | - Xiaoping Song
- College of Veterinary Medicine, Northwest A&F University, Yangling, China
- Xiaoping Song
| | - Jianxi Li
- Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China
- *Correspondence: Jianxi Li
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Comparative Evaluation of Plasma Metabolomic Data from Multiple Laboratories. Metabolites 2022; 12:metabo12020135. [PMID: 35208210 PMCID: PMC8877229 DOI: 10.3390/metabo12020135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 01/24/2022] [Accepted: 01/28/2022] [Indexed: 11/17/2022] Open
Abstract
In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.
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34
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Banerjee S, Prabhu Basrur N, Rai PS. Omics technologies in personalized combination therapy for cardiovascular diseases: challenges and opportunities. Per Med 2021; 18:595-611. [PMID: 34689602 DOI: 10.2217/pme-2021-0087] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The primary purpose of 'omics' technologies is to understand the intricacy of genomics, proteomics, metabolomics and other molecular mechanisms to reveal the complex traits of human diseases. The significant use of omics technologies and their applications in medicine gear up the study of the pathogenesis of several disorders. The detection of biomarkers in the early onset of diseases is challenging; still, omics can discover novel molecular mechanisms and biomarkers. In this review, the different types of omics and their technologies are explicated and aimed to provide their emerging applications in cardiovascular precision medicine. These technologies significantly impact optimizing medical treatment for individuals to reach a higher level in precision medicine.
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Affiliation(s)
- Saradindu Banerjee
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Navya Prabhu Basrur
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Padmalatha S Rai
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
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35
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SARS-CoV2 Infection Alters Tryptophan Catabolism and Phospholipid Metabolism. Metabolites 2021; 11:metabo11100659. [PMID: 34677374 PMCID: PMC8538244 DOI: 10.3390/metabo11100659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/24/2021] [Accepted: 09/24/2021] [Indexed: 12/22/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) has so far infected hundreds of million individuals, with several million deaths worldwide. The lack of understanding of the disease pathophysiology and the host’s immune response has resulted in this rapid spread of the disease on a global scale. In this respect, we employed UPLC-MS to compare the metabolites in the serum from COVID-19-positive patients and COVID-19-recovered subjects to determine the metabolic changes responsible for an infection. Our investigations revealed significant increase in the levels of serum phospholipids including sphingomyelins, phosphatidylcholines and arachidonic acid in the serum of COVID-19-positive patients as compared to COVID-19-recovered individuals. We further show increased levels of tryptophan and its metabolites in the serum of COVID-19-positive patients thus emphasizing the role of tryptophan metabolism in the disease pathogenesis of COVID-19. Future studies are required to determine the changes in the lipid and tryptophan metabolism at various stages of COVID-19 disease development, progression and recovery to better understand the host–pathogen interaction and the long-term effects of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in humans.
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36
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Beuchel C, Kirsten H, Ceglarek U, Scholz M. Metabolite-Investigator: an integrated user-friendly workflow for metabolomics multi-study analysis. Bioinformatics 2021; 37:2218-2220. [PMID: 33196775 PMCID: PMC8352501 DOI: 10.1093/bioinformatics/btaa967] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/13/2020] [Accepted: 11/04/2020] [Indexed: 12/04/2022] Open
Abstract
Motivation Many diseases have a metabolic background, which is increasingly investigated due to improved measurement techniques allowing high-throughput assessment of metabolic features in several body fluids. Integrating data from multiple cohorts is of high importance to obtain robust and reproducible results. However, considerable variability across studies due to differences in sampling, measurement techniques and study populations needs to be accounted for. Results We present Metabolite-Investigator, a scalable analysis workflow for quantitative metabolomics data from multiple studies. Our tool supports all aspects of data pre-processing including data integration, cleaning, transformation, batch analysis as well as multiple analysis methods including uni- and multivariable factor-metabolite associations, network analysis and factor prioritization in one or more cohorts. Moreover, it allows identifying critical interactions between cohorts and factors affecting metabolite levels and inferring a common covariate model, all via a graphical user interface. Availability and implementation We constructed Metabolite-Investigator as a free and open web-tool and stand-alone Shiny-app. It is hosted at https://apps.health-atlas.de/metabolite-investigator/, the source code is freely available at https://github.com/cfbeuchel/Metabolite-Investigator. Supplementary information Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Carl Beuchel
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, 04107 Leipzig, Germany
| | - Holger Kirsten
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, 04107 Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, 04103 Leipzig, Germany
| | - Uta Ceglarek
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, 04103 Leipzig, Germany
| | - Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, 04107 Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, 04103 Leipzig, Germany.,IFB AdiposityDiseases, University Hospital Leipzig, 04103 Leipzig, Germany
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37
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Ma S, Xia M, Gao X. Biomarker Discovery in Atherosclerotic Diseases Using Quantitative Nuclear Magnetic Resonance Metabolomics. Front Cardiovasc Med 2021; 8:681444. [PMID: 34395555 PMCID: PMC8356911 DOI: 10.3389/fcvm.2021.681444] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/02/2021] [Indexed: 12/23/2022] Open
Abstract
Despite great progress in the management of atherosclerosis (AS), its subsequent cardiovascular disease (CVD) remains the leading cause of morbidity and mortality. This is probably due to insufficient risk detection using routine lipid testing; thus, there is a need for more effective approaches relying on new biomarkers. Quantitative nuclear magnetic resonance (qNMR) metabolomics is able to phenotype holistic metabolic changes, with a unique advantage in regard to quantifying lipid-protein complexes. The rapidly increasing literature has indicated that qNMR-based lipoprotein particle number, particle size, lipid components, and some molecular metabolites can provide deeper insight into atherogenic diseases and could serve as novel promising determinants. Therefore, this article aims to offer an updated review of the qNMR biomarkers of AS and CVD found in epidemiological studies, with a special emphasis on lipoprotein-related parameters. As more researches are performed, we can envision more qNMR metabolite biomarkers being successfully translated into daily clinical practice to enhance the prevention, detection and intervention of atherosclerotic diseases.
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Affiliation(s)
- Shuai Ma
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Shanghai, China
- Human Phenome Institute, Fudan University, Shanghai, China
| | - Mingfeng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Shanghai, China
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38
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On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update. Biomolecules 2021; 11:biom11070971. [PMID: 34356595 PMCID: PMC8301931 DOI: 10.3390/biom11070971] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/23/2021] [Accepted: 06/29/2021] [Indexed: 02/08/2023] Open
Abstract
Infectious and many non-infectious diseases share common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins, and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, both produce metabolic alterations that influence the pathogenesis of the disease. In this review, we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, inducing migration and infiltration of immune cells in target tissues and disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.
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Salvia miltiorrhiza and the Volatile of Dalbergia odorifera Attenuate Chronic Myocardial Ischemia Injury in a Pig Model: A Metabonomic Approach for the Mechanism Study. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:8840896. [PMID: 34007406 PMCID: PMC8099511 DOI: 10.1155/2021/8840896] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 03/31/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023]
Abstract
Salvia miltiorrhiza (SM) coupled with Dalbergia odorifera (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM—the volatile oil of DO (SM-DOO)—has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.
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40
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Ishibashi Y, Harada S, Takeuchi A, Iida M, Kurihara A, Kato S, Kuwabara K, Hirata A, Shibuki T, Okamura T, Sugiyama D, Sato A, Amano K, Hirayama A, Sugimoto M, Soga T, Tomita M, Takebayashi T. Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry. Sci Rep 2021; 11:7407. [PMID: 33795760 PMCID: PMC8016858 DOI: 10.1038/s41598-021-86600-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/17/2021] [Indexed: 12/19/2022] Open
Abstract
Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.
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Affiliation(s)
- Yoshiki Ishibashi
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Sei Harada
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.,Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Ayano Takeuchi
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Miho Iida
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Ayako Kurihara
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Suzuka Kato
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Kazuyo Kuwabara
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Aya Hirata
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Takuma Shibuki
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Tomonori Okamura
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan
| | - Daisuke Sugiyama
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.,Faculty of Nursing And Medical Care, Keio University, Fujisawa, Kanagawa, Japan
| | - Asako Sato
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Kaori Amano
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Akiyoshi Hirayama
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Masahiro Sugimoto
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
| | - Tomoyoshi Soga
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.,Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, Japan
| | - Masaru Tomita
- Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.,Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, Japan
| | - Toru Takebayashi
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan. .,Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan.
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41
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Han X, Wang H, Li Y, Liu L, Gao S. A 2 miRNAs-based signature for the diagnosis of atherosclerosis. BMC Cardiovasc Disord 2021; 21:150. [PMID: 33761890 PMCID: PMC7988968 DOI: 10.1186/s12872-021-01960-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Atherosclerosis (AS) is a leading cause of vascular disease worldwide. MicroRNAs (miRNAs) play an essential role in the development of AS. However, the miRNAs-based biomarkers for the diagnosis of AS are still limited. Here, we aimed to identify the miRNAs significantly related to AS and construct the predicting model based on these miRNAs for distinguishing the AS patients from healthy cases. METHODS The miRNA and mRNA expression microarray data of blood samples from patients with AS and healthy cases were obtained from the GSE59421 and GSE20129 of Gene Expression Omnibus (GEO) database, respectively. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to evaluate the correlation of the miRNAs and mRNAs with AS and identify the miRNAs and mRNAs significantly associated with AS. The potentially critical miRNAs were further optimized by functional enrichment analysis. The logistic regression models were constructed based on these optimized miRNAs and validated by threefold cross-validation method. RESULTS WGCNA revealed 42 miRNAs and 532 genes significantly correlated with AS. Functional enrichment analysis identified 12 crucial miRNAs in patients with AS. Moreover, 6 miRNAs among the identified 12 miRNAs, were selected using a stepwise regression model, in which four miRNAs, including hsa-miR-654-5p, hsa-miR-409-3p, hsa-miR-485-5p and hsa-miR-654-3p, were further identified through multivariate regression analysis. The threefold cross-validation method showed that the AUC of logistic regression model based on the four miRNAs was 0.7308, 0.8258, and 0.7483, respectively, with an average AUC of 0.7683. CONCLUSION We identified a total of four miRNAs, including hsa-miR-654-5p and hsa-miR-409-3p, are identified as the potentially critical biomarkers for AS. The logistic regression model based on the identified 2 miRNAs could reliably distinguish the patients with AS from normal cases.
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Affiliation(s)
- Xiujiang Han
- Department of Geriatrics, Tianjin NanKai Hospital, No. 6 Changjiang Road, Nankai District, Tianjin City, 300100, China
| | - Huimin Wang
- Department of Neurology, Tianjin NanKai Hospital, Tianjin City, 300100, China
| | - Yongjian Li
- First Department of Cardiovascular Medicine, Tianjin NanKai Hospital, Tianjin City, 300100, China
| | - Lina Liu
- Department of Geriatrics, Tianjin NanKai Hospital, No. 6 Changjiang Road, Nankai District, Tianjin City, 300100, China
| | - Sheng Gao
- Nankai University, No. 94 Weijin Road, Nankai District, Tianjin City, 300071, China.
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42
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Liu MN, Luo G, Gao WJ, Yang SJ, Zhou H. miR-29 family: A potential therapeutic target for cardiovascular disease. Pharmacol Res 2021; 166:105510. [PMID: 33610720 DOI: 10.1016/j.phrs.2021.105510] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 02/16/2021] [Indexed: 01/11/2023]
Abstract
Cardiovascular disease (CVD), including heart failure, myocardial fibrosis and myocardial infarction, etc, remains one of the leading causes of mortality worldwide. Evidence shows that miRNA plays an important role in the pathogenesis of CVD. miR-29 family is one of miRNA, and over the past decades, many studies have demonstrated that miR-29 is involved in maintaining the integrity of arteries and in the regulation of atherosclerosis, especially in the process of myocardial fibrosis. Besides, heart failure, myocardial fibrosis and myocardial infarction are inseparable from the regulatory role of miR-29. Here, we comprehensively review recent studies regarding miR-29 and CVD, illustrate the possibility of miR-29 as a potential marker for prevention, treatment and prognostic observation.
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Affiliation(s)
- Meng-Nan Liu
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China; National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China
| | - Gang Luo
- National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China
| | - Wan-Jiao Gao
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China
| | - Si-Jin Yang
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China; National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, Sichuan, China.
| | - Hua Zhou
- Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China.
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43
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Cao H, Su S, Yang Q, Le Y, Chen L, Hu M, Guo X, Zheng J, Li X, Yu Y. Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients. Lipids Health Dis 2021; 20:16. [PMID: 33602246 PMCID: PMC7890626 DOI: 10.1186/s12944-021-01441-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/02/2021] [Indexed: 12/20/2022] Open
Abstract
Background Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear. Methods Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. Results A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment. Conclusion The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-021-01441-9.
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Affiliation(s)
- Han Cao
- School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China
| | - Shengmin Su
- School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China
| | - Qi Yang
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China
| | - Yunchen Le
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China
| | - Lihong Chen
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China
| | - Mengyan Hu
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China
| | - Xiaoyu Guo
- School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China
| | - Jie Zheng
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China
| | - Xia Li
- Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, People's Republic of China.
| | - Yunqiu Yu
- School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China.
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Liu C, Li R, Liu Y, Li Z, Sun Y, Yin P, Huang R. Characteristics of Blood Metabolic Profile in Coronary Heart Disease, Dilated Cardiomyopathy and Valvular Heart Disease Induced Heart Failure. Front Cardiovasc Med 2021; 7:622236. [PMID: 33553267 PMCID: PMC7856915 DOI: 10.3389/fcvm.2020.622236] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 12/23/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose: Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations. Procedure: In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach. Results: Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts. Conclusion: This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.
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Affiliation(s)
- Chang Liu
- First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ruihua Li
- Medical Laboratory Science, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yang Liu
- First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zhenguo Li
- Medical Laboratory Science, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yujiao Sun
- First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Peiyuan Yin
- First Affiliated Hospital of Dalian Medical University, Dalian, China.,College of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Rihong Huang
- First Affiliated Hospital of Dalian Medical University, Dalian, China
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Audano M, Pedretti S, Ligorio S, Giavarini F, Caruso D, Mitro N. Investigating metabolism by mass spectrometry: From steady state to dynamic view. JOURNAL OF MASS SPECTROMETRY : JMS 2021; 56:e4658. [PMID: 33084147 DOI: 10.1002/jms.4658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/10/2020] [Accepted: 09/14/2020] [Indexed: 06/11/2023]
Abstract
Metabolism is the set of life-sustaining reactions in organisms. These biochemical reactions are organized in metabolic pathways, in which one metabolite is converted through a series of steps catalyzed by enzymes in another chemical compound. Metabolic reactions are categorized as catabolic, the breaking down of metabolites to produce energy, and/or anabolic, the synthesis of compounds that consume energy. The balance between catabolism of the preferential fuel substrate and anabolism defines the overall metabolism of a cell or tissue. Metabolomics is a powerful tool to gain new insights contributing to the identification of complex molecular mechanisms in the field of biomedical research, both basic and translational. The enormous potential of this kind of analyses consists of two key aspects: (i) the possibility of performing so-called targeted and untargeted experiments through which it is feasible to verify or formulate a hypothesis, respectively, and (ii) the opportunity to run either steady-state analyses to have snapshots of the metabolome at a given time under different experimental conditions or dynamic analyses through the use of labeled tracers. In this review, we will highlight the most important practical (e.g., different sample extraction approaches) and conceptual steps to consider for metabolomic analysis, describing also the main application contexts in which it is used. In addition, we will provide some insights into the most innovative approaches and progress in the field of data analysis and processing, highlighting how this part is essential for the proper extrapolation and interpretation of data.
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Affiliation(s)
- Matteo Audano
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
| | - Silvia Pedretti
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
| | - Simona Ligorio
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
| | - Flavio Giavarini
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
| | - Donatella Caruso
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
| | - Nico Mitro
- DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, 20133, Italy
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Cheng CF, Ku HC, Shen TC. The potential of using itaconate as treatment for inflammation-related heart diseases. Tzu Chi Med J 2021; 34:113-118. [PMID: 35465278 PMCID: PMC9020236 DOI: 10.4103/tcmj.tcmj_83_21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/03/2021] [Accepted: 06/07/2021] [Indexed: 11/04/2022] Open
Abstract
Intracellular metabolites can cause critical changes in biological functions. Itaconate is perhaps the most fascinating substance in macrophages. Lipopolysaccharide can activate aconitate decarboxylase 1 and induces the generation of itaconate from the tricarboxylic acid cycle by decarboxylation of cis-aconitate. It has been reported that itaconate has beneficial effects on inflammation and oxidation. The mechanisms involved in these effects include the suppression of succinate dehydrogenase, the activation of nuclear factor E2-related factor 2 by alkylation of Kelch-like ECH-associated protein 1, suppression of aerobic glycolysis through regulation of glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase A, and suppression of IκBζ translation through activating transcription factor 3 activation. All of these findings elucidated the possible therapeutic implications of itaconate in inflammation-related diseases. In this review, we highlight that itaconate is a crucial molecule of the immunomodulatory response in macrophages and can regulate between immune response and cardiovascular metabolism. Furthermore, these discoveries suggest that itaconate is a very novel therapeutic molecule for the treatment of inflammation-related heart diseases.
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Ashrafian H, Sounderajah V, Glen R, Ebbels T, Blaise BJ, Kalra D, Kultima K, Spjuth O, Tenori L, Salek RM, Kale N, Haug K, Schober D, Rocca-Serra P, O'Donovan C, Steinbeck C, Cano I, de Atauri P, Cascante M. Metabolomics: The Stethoscope for the Twenty-First Century. Med Princ Pract 2020; 30:301-310. [PMID: 33271569 PMCID: PMC8436726 DOI: 10.1159/000513545] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/29/2020] [Indexed: 11/19/2022] Open
Abstract
Metabolomics encompasses the systematic identification and quantification of all metabolic products in the human body. This field could provide clinicians with novel sets of diagnostic biomarkers for disease states in addition to quantifying treatment response to medications at an individualized level. This literature review aims to highlight the technology underpinning metabolic profiling, identify potential applications of metabolomics in clinical practice, and discuss the translational challenges that the field faces. We searched PubMed, MEDLINE, and EMBASE for primary and secondary research articles regarding clinical applications of metabolomics. Metabolic profiling can be performed using mass spectrometry and nuclear magnetic resonance-based techniques using a variety of biological samples. This is carried out in vivo or in vitro following careful sample collection, preparation, and analysis. The potential clinical applications constitute disruptive innovations in their respective specialities, particularly oncology and metabolic medicine. Outstanding issues currently preventing widespread clinical use are scalability of data interpretation, standardization of sample handling practice, and e-infrastructure. Routine utilization of metabolomics at a patient and population level will constitute an integral part of future healthcare provision.
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Affiliation(s)
- Hutan Ashrafian
- Institute of Global Health Innovation and Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Viknesh Sounderajah
- Institute of Global Health Innovation and Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Robert Glen
- Institute of Global Health Innovation and Department of Surgery and Cancer, Imperial College London, London, United Kingdom
- Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom
| | - Timothy Ebbels
- Institute of Global Health Innovation and Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Benjamin J. Blaise
- Institute of Global Health Innovation and Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Dipak Kalra
- Department of Medical Informatics and Statistics, University of Ghent, Ghent, Belgium
| | - Kim Kultima
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Ola Spjuth
- Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
| | - Leonardo Tenori
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Reza M. Salek
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
| | - Namrata Kale
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
| | - Kenneth Haug
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
| | - Daniel Schober
- Department of Stress and Developmental Biology, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany
| | - Philippe Rocca-Serra
- Department of Engineering Science, Oxford e-Research Centre, University of Oxford, Oxford, United Kingdom
| | - Claire O'Donovan
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
| | - Christoph Steinbeck
- Institute for Inorganic and Analytical Chemistry, Friedrich-Schiller-University, Jena, Germany
| | - Isaac Cano
- Hospital Clinic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Pedro de Atauri
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona and CIBERHD (CIBER de Enfermedades hepáticas y digestivas), Barcelona, Spain
| | - Marta Cascante
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona and CIBERHD (CIBER de Enfermedades hepáticas y digestivas), Barcelona, Spain
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李 妙, 钱 少, 姚 卓, 闵 生, 史 晓, 康 品, 张 宁, 王 效, 高 大, 高 琴, 张 恒, 王 洪. [Correlation of plasma N-acetyl-neuraminic acid level with TIMI risk stratification and clinical outcomes in patients with acute coronary syndrome]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2020; 40:1253-1258. [PMID: 32990230 PMCID: PMC7544578 DOI: 10.12122/j.issn.1673-4254.2020.09.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To explore the correlation of plasma N-acetyl-neuraminic acid level with Thrombolysis In Myocardial Infarction (TIMI) risk score and clinical outcomes of patients with acute coronary syndrome (ACS). METHODS We consecutively enrolled 708 consecutive patients (401 male and 307 female, mean age 63.6±10.6 years) undergoing coronary angiography in our hospital between October, 2018 and July, 2019, including 597 patients with ACS and 111 without ACS (control group). The patients with ACS group were divided into high (n=104), moderate (n=425) and low (n=68) risk groups according to their TIMI risk scores. All the participants were examined for plasma Neu5Ac level using liquid chromatography-tandem mass spectrometry and underwent coronary angiography with their Gensini scores calculated. The patients with ACS were followed up after discharge for a mean of 15 months for the occurrence of major adverse cardiac events (Mace). Binary logistic regression analysis was performed to identify the risk factors of Mace in these patients. RESULTS Plasma Neu5Ac levels were significantly higher in ACS group than in the control group (P < 0.05). ROC curve analysis showed that plasma Neu5Ac level could assist in the diagnosis of ACS (0.648 [0.597-0.699]) with a sensitivity of 39.2% and a specificity of 86.5% at the cutoff value of 288.50 ng/mL. In the ACS patients, plasma Neu5Ac level was significantly higher in the high-risk group than in the moderate-risk and low-risk groups (P < 0.05) and could assist in the diagnosis of a high risk (0.645 [0.588-0.703]) with a sensitivity of 42.3% and a specificity of 80.1% at the cutoff value of 327.50 ng/ mL. Plasma Neu5Ac was positively correlated with age, serum uric acid, creatinine, lipoprotein a, Ddimer, C-reactive protein, MB isoform of creatine kinase and Gensini score and negatively correlated with high-density lipoprotein level. During the followup, 80 ACS patients experienced Mace, who had significantly higher plasma Neu5Ac level than those without Mace (n=517). Logistic regression analysis showed that plasma Neu5Ac level and a history of previous stroke were independent risk factors for the occurrence of Mace. CONCLUSIONS Plasma Neu5Ac level can provide assistance in the diagnosis and risk stratification of ACS and is an independent risk factor for prognosis of ACS patients.
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Affiliation(s)
- 妙男 李
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
- 蚌埠医学院第一附属医院山东大学齐鲁医学院，安徽 蚌埠 233004Cheeloo College of Medicine, Shangdong University, Bengbu 233004, China
| | - 少环 钱
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 卓亚 姚
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 生萍 闵
- 蚌埠医学院第一附属医院呼吸系病临床基础安徽省重点实验室，安徽 蚌埠 233004Anhui Clinical and Preclinical Key Laboratory of Respriatory Disease, Bengbu 233004, China
| | - 晓俊 史
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 品方 康
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 宁汝 张
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 效静 王
- 蚌埠医学院第一附属医院呼吸系病临床基础安徽省重点实验室，安徽 蚌埠 233004Anhui Clinical and Preclinical Key Laboratory of Respriatory Disease, Bengbu 233004, China
| | - 大胜 高
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 琴 高
- 蚌埠医学院第一附属医院数字医 学与智慧健康安徽省重点实验室，安徽 蚌埠 233004Anhui Provincial Key Laboratory of Computational Medicine and Intelligent Health, Bengbu 233004, China
| | - 恒 张
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
| | - 洪巨 王
- 蚌埠医学院第一附属医院心血管内科，安徽 蚌埠 233004Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
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Nik Mohd Fakhruddin NNI, Shahar S, Ismail IS, Ahmad Azam A, Rajab NF. Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly. Nutrients 2020; 12:nu12102900. [PMID: 32977370 PMCID: PMC7597952 DOI: 10.3390/nu12102900] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/30/2020] [Accepted: 09/02/2020] [Indexed: 01/06/2023] Open
Abstract
Food intake biomarkers (FIBs) can reflect the intake of specific foods or dietary patterns (DP). DP for successful aging (SA) has been widely studied. However, the relationship between SA and DP characterized by FIBs still needs further exploration as the candidate markers are scarce. Thus, 1H-nuclear magnetic resonance (1H-NMR)-based urine metabolomics profiling was conducted to identify potential metabolites which can act as specific markers representing DP for SA. Urine sample of nine subjects from each three aging groups, SA, usual aging (UA), and mild cognitive impairment (MCI), were analyzed using the 1H-NMR metabolomic approach. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied. The association between SA urinary metabolites and its DP was assessed using the Pearson’s correlation analysis. The urine of SA subjects was characterized by the greater excretion of citrate, taurine, hypotaurine, serotonin, and melatonin as compared to UA and MCI. These urinary metabolites were associated with alteration in “taurine and hypotaurine metabolism” and “tryptophan metabolism” in SA elderly. Urinary serotonin (r = 0.48, p < 0.05) and melatonin (r = 0.47, p < 0.05) were associated with oat intake. These findings demonstrate that a metabolomic approach may be useful for correlating DP with SA urinary metabolites and for further understanding of SA development.
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Affiliation(s)
- Nik Nur Izzati Nik Mohd Fakhruddin
- Dietetic Programme, Centre for Healthy Aging and Wellness (H-CARE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
| | - Suzana Shahar
- Dietetic Programme, Centre for Healthy Aging and Wellness (H-CARE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
- Correspondence: ; Tel.: +60-3-9289-7602; Fax: +60-3-9289-7161
| | - Intan Safinar Ismail
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia; (I.S.I.); (A.A.A.)
| | - Amalina Ahmad Azam
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia; (I.S.I.); (A.A.A.)
| | - Nor Fadilah Rajab
- Biomedical Science Programme, Centre for Healthy Ageing and Wellness (H-CARE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
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Plasma Metabolic Signature of Atherosclerosis Progression and Colchicine Treatment in Rabbits. Sci Rep 2020; 10:7072. [PMID: 32341369 PMCID: PMC7184732 DOI: 10.1038/s41598-020-63306-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 03/30/2020] [Indexed: 01/02/2023] Open
Abstract
Balloon catheter endothelial denudation in New Zealand white rabbits fed high cholesterol diet is a validated atherosclerosis model. Well-characterized in terms of atherosclerosis induction and progression, the metabolic changes associated with the atherosclerosis progression remain indeterminate. Non-targeted metabolomics permits to develop such elucidation and allows to evaluate the metabolic consequences of colchicine treatment, an anti-inflammatory drug that could revert these changes. 16 rabbits underwent 18 weeks of atherosclerosis induction by diet and aortic denudation. Thereafter animals were randomly assigned to colchicine treatment or placebo for 18 weeks while on diet. Plasma samples were obtained before randomization and at 36 weeks. Multiplatform (GC/MS, CE/MS, RP-HPLC/MS) metabolomics was applied. Plasma fingerprints were pre-processed, and the resulting matrixes analyzed to unveil differentially expressed features. Different chemical annotation strategies were accomplished for those significant features. We found metabolites associated with either atherosclerosis progression, or colchicine treatment, or both. Atherosclerosis was profoundly associated with an increase in circulating bile acids. Most of the changes associated with sterol metabolism could not be reverted by colchicine treatment. However, the variations in lysine, tryptophan and cysteine metabolism among others, have shown new potential mechanisms of action of the drug, also related to atherosclerosis progression, but not previously described.
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