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Nomura SO, Bhatia HS, Garg PK, Karger AB, Guan W, Cao J, Shapiro MD, Tsai MY. Lipoprotein(a), high-sensitivity c-reactive protein, homocysteine and cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Am J Prev Cardiol 2025; 21:100903. [PMID: 39802678 PMCID: PMC11722194 DOI: 10.1016/j.ajpc.2024.100903] [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: 08/14/2024] [Revised: 11/26/2024] [Accepted: 12/01/2024] [Indexed: 01/16/2025] Open
Abstract
Background and aims Elevated lipoprotein(a) [Lp(a)], high-sensitivity C-Reactive Protein (hs-CRP), and total homocysteine (tHcy) are associated with atherosclerotic cardiovascular disease (ASCVD) risk. This study investigated the individual and joint associations of Lp(a), hs-CRP and tHcy with coronary heart disease (CHD) and stroke. Methods This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (2000-2017) (CHD analytic N = 6,676; stroke analytic N = 6,674 men and women). Associations between Lp(a) (<50 vs. ≥50 mg/dL), hs-CRP (<2 vs. ≥2 mg/L) and tHcy (<12 vs. ≥12 µmol/L) and CHD and stroke incidence were evaluated individually and jointly using Cox proportional hazards regression. Results Individually, elevated tHcy was associated with CHD and stroke incidence, Lp(a) with CHD only and hs-CRP with stroke only. In combined analyses, CHD risk was higher when multiple biomarkers were elevated [hs-CRP+Lp(a), hazard ratio (HR)=1.39, 95 % confidence interval (CI): 1.06, 1.82; hs-CRP+ tHcy, HR = 1.34, 95 % CI: 1.02, 1.75; Lp(a)+ tHcy HR = 1.58, 95 % CI: 1.08, 2.30; hs-CRP+Lp(a)+ tHcy HR = 2.02, 95 % CI: 1.26, 3.24]. Stroke risk was elevated when hs-CRP and either Lp(a) (HR = 1.51, 95 % CI: 1.02, 2.23) or tHcy (HR = 2.10, 95 % CI: 1.44, 3.06) was also high, when all three biomarkers were elevated (HR = 2.99, 95 % CI: 1.61, 5.58), or when hs-CRP and tHcy (HR = 1.79, 95 % CI: 1.16, 2.76) were both high. Conclusions Risk of ASCVD was highest with concomitant elevation of tHcy, hs-CRP and Lp(a). Inclusion of tHcy and consideration of biomarker combination rather than individual biomarker levels may help better identify individuals at greatest risk for ASCVD events.
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Affiliation(s)
- Sarah O. Nomura
- Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA
| | - Harpreet S. Bhatia
- Division of Cardiovascular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Parveen K. Garg
- Division of Cardiology, University of Southern California Keck School of Medicine, 1975 Zonal Ave., Los Angeles, CA 90033, USA
| | - Amy B. Karger
- Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA
| | - Weihua Guan
- School of Public Health Biostatistics Division, University of Minnesota, 420 Delaware St SE, MN, 55455, USA
| | - Jing Cao
- Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
| | - Michael D. Shapiro
- Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, 475 Vine Street, Winston-Salem, North Carolina 27101, USA
| | - Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA
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Qadir M, Aslam S, Lail Shah B, Akbar A, Jadoon SK. Hyperhomocysteinemia Causing Myocardial Infarction in a Young Patient: A Case Report. Cureus 2025; 17:e77421. [PMID: 39958020 PMCID: PMC11825229 DOI: 10.7759/cureus.77421] [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] [Accepted: 01/13/2025] [Indexed: 02/18/2025] Open
Abstract
Hyperhomocysteinemia is an independent risk factor for acute myocardial infarction (MI). This case report describes a 19-year-old male with a marfanoid phenotype and no conventional risk factors presenting with acute MI. It highlights the significance of acknowledging hyperhomocysteinemia as a potential risk factor for MI, especially in young patients.
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Affiliation(s)
- Mamoon Qadir
- Cardiology, Federal Government Poly Clinic, Islamabad, PAK
| | - Sabina Aslam
- Cardiology, Federal Government Poly Clinic, Islamabad, PAK
| | | | - Amna Akbar
- Emergency and Accident, District Headquarter Hospital Jhelum Valley, Muzaffarabad, PAK
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Mucha P, Kus F, Cysewski D, Smolenski RT, Tomczyk M. Vitamin B 12 Metabolism: A Network of Multi-Protein Mediated Processes. Int J Mol Sci 2024; 25:8021. [PMID: 39125597 PMCID: PMC11311337 DOI: 10.3390/ijms25158021] [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: 06/03/2024] [Revised: 07/12/2024] [Accepted: 07/19/2024] [Indexed: 08/12/2024] Open
Abstract
The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.
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Affiliation(s)
- Patryk Mucha
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
| | - Filip Kus
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
- Laboratory of Protein Biochemistry, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland
| | - Dominik Cysewski
- Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Ryszard T. Smolenski
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
| | - Marta Tomczyk
- Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland; (P.M.); (F.K.); (R.T.S.)
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Marongiu F, Ruberto MF, Marongiu S, Mameli A, Barcellona D. Do we need more guidance on thrombophilia testing? Challenges and special considerations. Expert Rev Hematol 2024; 17:27-37. [PMID: 38228491 DOI: 10.1080/17474086.2024.2306821] [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: 11/23/2023] [Accepted: 01/15/2024] [Indexed: 01/18/2024]
Abstract
INTRODUCTION Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also controversial because it has a limited impact on the choice and duration of antithrombotic treatments. AREAS COVERED We reviewed, by examining MEDLINE up to October 2023. Accepted and not accepted thrombophilia markers are discussed along with the appropriateness or not of prescribing TT in several conditions such as: provoked and unprovoked venous thromboembolism (VTE), women who are planning a pregnancy whose relatives had VTE or have a hereditary thrombophilia, before assumption of estro-progestins, after multiple pregnant loss, arterial thrombosis, retinal vein occlusion, and splanchnic vein thrombosis. EXPERT OPINION TT is not essential in the management of VTE, but it may be useful for limiting adverse events in case of thrombophilia. We expose our criticism of items afforded by other guidelines by presenting our opinion based on both the scientific evidence and clinical practice. We also deal with common mistakes in prescribing and interpretations of TT hoping to purpose an educational approach on this topic. Finally, we emphasize the creation of the expert in hemostasis and thrombosis who should be present in every hospital.
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Affiliation(s)
- Francesco Marongiu
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Haemostasis and Thrombosis Unit, Azienda Ospedaliera Universitaria of Cagliari, Cagliari, Italy
| | - Maria Filomena Ruberto
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Silvia Marongiu
- Internal Medicine department, SS Trinità Hospital, ASL, Cagliari, Italy
| | - Antonella Mameli
- Haemostasis and Thrombosis Unit, Azienda Ospedaliera Universitaria of Cagliari, Cagliari, Italy
| | - Doris Barcellona
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Haemostasis and Thrombosis Unit, Azienda Ospedaliera Universitaria of Cagliari, Cagliari, Italy
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Quan Y, Xu J, Xu Q, Guo Z, Ou R, Shang H, Wei Q. Association between the risk and severity of Parkinson's disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis. Front Aging Neurosci 2023; 15:1254824. [PMID: 37941998 PMCID: PMC10628521 DOI: 10.3389/fnagi.2023.1254824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/25/2023] [Indexed: 11/10/2023] Open
Abstract
Background Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence. Methods Suitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1. Results The results of our meta-analysis, consisting of case-control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: -0.30[-0.39, -0.22], p < 0.001 for Vitamin B12; SMD [95%CI]: -0.20 [-0.28, -0.13], p < 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], p < 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], p < 0.001) rather than plasma Hcy below 15 μmol/L (SMD [95%]: -0.31 [-0.62, 0.00], p = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region (p = 0.03), age (p = 0.03), levodopa therapy (p = 0.03), Hoehn and Yahr stage (p < 0.001), and cognitive impairment (p < 0.001). However, gender (p = 0.38) and sample size (p = 0.49) were not associated. Conclusion Hcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.
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Affiliation(s)
- Yuxin Quan
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jisen Xu
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qing Xu
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhiqing Guo
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China
| | - Ruwei Ou
- Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Huifang Shang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qianqian Wei
- Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Cimmino G, Natale F, Alfieri R, Cante L, Covino S, Franzese R, Limatola M, Marotta L, Molinari R, Mollo N, Loffredo FS, Golino P. Non-Conventional Risk Factors: "Fact" or "Fake" in Cardiovascular Disease Prevention? Biomedicines 2023; 11:2353. [PMID: 37760794 PMCID: PMC10525401 DOI: 10.3390/biomedicines11092353] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/18/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
Cardiovascular diseases (CVDs), such as arterial hypertension, myocardial infarction, stroke, heart failure, atrial fibrillation, etc., still represent the main cause of morbidity and mortality worldwide. They significantly modify the patients' quality of life with a tremendous economic impact. It is well established that cardiovascular risk factors increase the probability of fatal and non-fatal cardiac events. These risk factors are classified into modifiable (smoking, arterial hypertension, hypercholesterolemia, low HDL cholesterol, diabetes, excessive alcohol consumption, high-fat and high-calorie diet, reduced physical activity) and non-modifiable (sex, age, family history, of previous cardiovascular disease). Hence, CVD prevention is based on early identification and management of modifiable risk factors whose impact on the CV outcome is now performed by the use of CV risk assessment models, such as the Framingham Risk Score, Pooled Cohort Equations, or the SCORE2. However, in recent years, emerging, non-traditional factors (metabolic and non-metabolic) seem to significantly affect this assessment. In this article, we aim at defining these emerging factors and describe the potential mechanisms by which they might contribute to the development of CVD.
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Affiliation(s)
- Giovanni Cimmino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, 80138 Naples, Italy
| | - Francesco Natale
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Roberta Alfieri
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Luigi Cante
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Simona Covino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Rosa Franzese
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Mirella Limatola
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Luigi Marotta
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Riccardo Molinari
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Noemi Mollo
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Francesco S Loffredo
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
| | - Paolo Golino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy (F.S.L.)
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy
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Valls R, Wagg J, Paz-Priel I, Man G, Artigas L, Jaccard G, Coma M, Schmitt C. Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab. Sci Rep 2023; 13:10078. [PMID: 37344529 DOI: 10.1038/s41598-023-36891-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 06/12/2023] [Indexed: 06/23/2023] Open
Abstract
Emicizumab is a bispecific monoclonal antibody that substitutes for the function of missing or deficient factor VIII (FVIII) in people with hemophilia A (PwHA). Long-term safety and efficacy of emicizumab have been demonstrated in several clinical trials. Nevertheless, in the first of these, three cases of thrombotic microangiopathy (TMA) occurred in PwHA treated with emicizumab receiving high doses of activated prothrombin complex concentrate (aPCC), a bypassing agent used for treating breakthrough bleeds when FVIII neutralizing antibodies (inhibitors) make FVIII replacement ineffective. The aim of the present work is to offer a method to elucidate the pathophysiological and pharmacological mechanisms involved in this treatment-induced TMA. Systems biology and machine learning-based Therapeutic Performance Mapping System is a validated in silico technology that allowed us to construct models of potential mechanisms behind induced TMA. Two drug combinations were modeled and assessed: emicizumab plus aPCC and emicizumab plus recombinant activated factor VII (another bypassing agent). Our models showed that both combinations were related to activation of the coagulation cascade. However, mechanisms involved mainly in platelet activation and possibly in complement activation were detected only for emicizumab plus aPCC, potentially explaining the occurrence of TMA only in this combination.
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Affiliation(s)
| | - Jonathan Wagg
- Roche Innovation Center, Basel, Switzerland
- AC Immune SA, EPFL Innovation Park, Lausanne, Switzerland
| | - Ido Paz-Priel
- Genentech, Inc., South San Francisco, CA, USA
- Graphite Bio Inc., South San Francisco, CA, USA
| | - Gabriel Man
- Genentech, Inc., South San Francisco, CA, USA
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Yu B, Zhang B, Han X, Long W, Zhou W, Yuan X. Platelet counts affect the association between hyperhomocysteinemia and pregnancy complications. BMC Public Health 2023; 23:1058. [PMID: 37268909 PMCID: PMC10236586 DOI: 10.1186/s12889-023-16027-6] [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: 02/07/2023] [Accepted: 05/31/2023] [Indexed: 06/04/2023] Open
Abstract
BACKGROUND The joint effect of platelet and other modifiers on the risk of pregnancy complications is unknown. This study investigated whether platelet count (PC) and total homocysteine (tHcy) level have a synergistic effect on the incidence of pregnancy complications in a Chinese population. METHODS Total 11,553 consecutive pregnant women who received whole blood cell and biochemical tests at the time of admission for labor in Changzhou Maternal and Child Health Care Hospital were analyzed. The primary outcome was the prevalence of pregnancy complications: gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), pre-eclampsia (PE), and pregnancy induced hypertension (PIH). RESULTS The prevalence of GDM, ICP, PE, and PIH was 8.4%, 6.2%, 3.4%, and 2.1%, respectively. The highest rate of ICP (28.6%) was observed in women with high tHcy (> 15 μmol/L) and low PC (quartile 1); and the lowest rate of GDM (0.6%) was found in women with high tHcy and high PC (quartiles 2 to 4). In low PC group, the prevalence of ICP in women with high tHcy was significantly higher than that in women with low tHcy (≤ 15 μmol/L) (28.6% vs. 8.4%), representing an absolute risk increment of 20.2% and a relative risk increment of 3.3-fold (OR: 3.34; 95% CI: 1.55, 7.17; P = 0.002), whereas no joint effect was observed among high PC group. CONCLUSIONS Among Chinese pregnant women, one subgroup (high tHcy and low PC) has the highest risk of ICP and another (high tHcy and high PC) has the lowest risk of GDM; tHcy and platelet could be used as indicators to identify the women with high risk of ICP or low risk of GDM.
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Affiliation(s)
- Bin Yu
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
| | - Bin Zhang
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
| | - Xiaoya Han
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
| | - Wei Long
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
| | - Wenbo Zhou
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
| | - Xiaosong Yuan
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16th Ding Xiang Road, Changzhou, 213023 Jiangsu China
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Yang X, Tian X, Liu H, Wang J, Wang F. Homocysteine increases uterine artery blood flow resistance in women with pregnancy loss. J Gynecol Obstet Hum Reprod 2023; 52:102533. [PMID: 36610604 DOI: 10.1016/j.jogoh.2023.102533] [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: 06/07/2022] [Revised: 09/08/2022] [Accepted: 01/01/2023] [Indexed: 01/06/2023]
Abstract
OBJECTIVE Uterine arterial blood flow is an important factor in embryonic development. Increased uterine artery blood flow resistance may be related to vascular damage. Homocysteine (HCY) can induce injury of endothelial through various pathways. Therefore, we investigate the association between serum HCY levels and uterine artery blood flow in the non-pregnant state in women who have experienced pregnancy loss (PL). METHODS 364 women eligible for PL were included in the study. The detection of HCY was completed by the Laboratory of Lanzhou University Second Hospital. We divided the patients into three groups: Low-HCY (HCY<10 umol/L, n = 144), Medium-HCY (HCY 10∼15 umol/L, n = 174) and High-HCY (HCY>15 umol/L, n = 46). The patients were subjected to vaginal color Doppler ultrasonography to measure bilateral uterine artery resistance index (RI), pulsatility index (PI) and peak systolic velocity/end diastolic velocity (S/D). RESULT Among 364 women, the right uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.79±0.07 and 0.81±0.07, respectively (P = 0.04). The left uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.81±0.07 and 0.81±0.07, respectively (P = 0.01). The right uterine artery RI level and the left uterine artery RI was significantly associated with HCY level (r = 0.103, P = 0.050; r = 0.104, P = 0.047, respectively). Of these, 177 women experienced their next pregnancy, and 33 patients experienced PL again. The pregnancy rate in l-HCY, M-HCY, and HHCY groups were 47.92% (69/144), 49.43% (86/174) and 47.83% (22/46), respectively (P = 0.95). In next pregnancy, the PL rate in l-HCY, M-HCY, and HHCY groups were 8.70% (6/69), 22.58% (22/86) and 22.73% (5/22), respectively (P = 0.03). CONCLUSION HCY can increase the uterine artery resistance in the non-pregnant state and is associated with the abortion rate of next pregnancy.
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Affiliation(s)
- Xin Yang
- Reproductive Medicine Center, Second Hospital of Lanzhou University, No.82, Cuiying Road, Chengguan District, Lanzhou, Gansu 730030, China
| | - Xiuli Tian
- Reproductive Medicine Center, Second Hospital of Lanzhou University, No.82, Cuiying Road, Chengguan District, Lanzhou, Gansu 730030, China
| | - Haoxin Liu
- College of LSA, University of Michigan, Ann Arbor, MI 48109, United States
| | - Juan Wang
- Reproductive Medicine Center, Second Hospital of Lanzhou University, No.82, Cuiying Road, Chengguan District, Lanzhou, Gansu 730030, China
| | - Fang Wang
- Reproductive Medicine Center, Second Hospital of Lanzhou University, No.82, Cuiying Road, Chengguan District, Lanzhou, Gansu 730030, China.
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Li J, Zhang J, Chen Y, Gao L, Yan X, Zhang M, Wang F, He Y, Hu W, Peng H. Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study. Nutr Metab Cardiovasc Dis 2023; 33:194-202. [PMID: 36404241 DOI: 10.1016/j.numecd.2022.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/04/2022] [Accepted: 10/26/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND AND AIMS The effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. METHODS AND RESULTS A total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06-0.45). CONCLUSIONS The association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.
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Affiliation(s)
- Jing Li
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Jianan Zhang
- Department of Chronic Disease Management, Taicang Center for Disease Prevention and Control, Taicing, China
| | - Yan Chen
- Department of Nephrology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, China
| | - Linglin Gao
- Department of Chronic Disease Management, Taicang Center for Disease Prevention and Control, Taicing, China
| | - Xiaoluan Yan
- Department of Chronic Disease Management, Taicang Center for Disease Prevention and Control, Taicing, China
| | - Mingzhi Zhang
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Fenchun Wang
- Department of Chronic Disease Management, Taicang Center for Disease Prevention and Control, Taicing, China
| | - Yan He
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Weidong Hu
- Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
| | - Hao Peng
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou, China.
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11
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Michael M, Bagga A, Sartain SE, Smith RJH. Haemolytic uraemic syndrome. Lancet 2022; 400:1722-1740. [PMID: 36272423 DOI: 10.1016/s0140-6736(22)01202-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 06/16/2022] [Accepted: 06/16/2022] [Indexed: 11/05/2022]
Abstract
Haemolytic uraemic syndrome (HUS) is a heterogeneous group of diseases that result in a common pathology, thrombotic microangiopathy, which is classically characterised by the triad of non-immune microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. In this Seminar, different causes of HUS are discussed, the most common being Shiga toxin-producing Escherichia coli HUS. Identifying the underlying thrombotic microangiopathy trigger can be challenging but is imperative if patients are to receive personalised disease-specific treatment. The quintessential example is complement-mediated HUS, which once carried an extremely high mortality but is now treated with anti-complement therapies with excellent long-term outcomes. Unfortunately, the high cost of anti-complement therapies all but precludes their use in low-income countries. For many other forms of HUS, targeted therapies are yet to be identified.
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Affiliation(s)
- Mini Michael
- Division of Pediatric Nephrology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
| | - Arvind Bagga
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Sarah E Sartain
- Pediatrics-Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Richard J H Smith
- Department of Otolaryngology, Pediatrics and Molecular Physiology & Biophysics, The University of Iowa, Iowa City, IA, USA
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12
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Gala D, Newsome T, Roberson N, Lee SM, Thekkanal M, Shah M, Kumar V, Bandaru P, Gayam V. Thromboembolic Events in Patients with Inflammatory Bowel Disease: A Comprehensive Overview. Diseases 2022; 10:diseases10040073. [PMID: 36278572 PMCID: PMC9589934 DOI: 10.3390/diseases10040073] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/22/2022] [Accepted: 09/27/2022] [Indexed: 11/24/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of the intestines. The underlying inflammation activates the coagulation cascade leading to an increased risk of developing arterial and venous thromboembolic events such as deep vein thrombosis and pulmonary embolism. Patients with IBD are at a 2–3-fold increased risk of developing thromboembolism. This risk increases in patients with active IBD disease, flare-ups, surgery, steroid treatment, and hospitalization. These complications are associated with significant morbidity and mortality making them important in clinical practice. Clinicians should consider the increased risk of thromboembolic events in patients with IBD and manage them with appropriate prophylaxis based on the risk. In this review, we discuss the literature associated with the pathophysiology of thromboembolism in patients with IBD, summarize the studies describing the various thromboembolic events, and the management of thromboembolism in patients with IBD.
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Affiliation(s)
- Dhir Gala
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
- Correspondence:
| | - Taylor Newsome
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Nicole Roberson
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Soo Min Lee
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Marvel Thekkanal
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Mili Shah
- American University of the Caribbean School of Medicine, 1 University Drive at Jordan Dr, Cupecoy, Sint Maarten, The Netherlands
| | - Vikash Kumar
- Department of Internal Medicine, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
| | - Praneeth Bandaru
- Department of Gastroenterology, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
| | - Vijay Gayam
- Department of Gastroenterology, The Brooklyn Hospital Center, 121 DeKalb Ave, Brooklyn, NY 11201, USA
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13
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Relationships of Serum Homocysteine, Vitamin B12, and Folic Acid Levels with Papulopustular Rosacea Severity: A Case-Control Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5479626. [PMID: 35832851 PMCID: PMC9273444 DOI: 10.1155/2022/5479626] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 06/18/2022] [Indexed: 02/07/2023]
Abstract
Background Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin B12 in patients with rosacea. Objective To investigate serum Hcy, vitamin B12, and folic acid levels in patients with papulopustular rosacea (PPR), we characterized the association of these levels with PPR severity. Methods This case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin B12, and folic acid were measured. A correlation was assessed between disease severity and serum levels of Hcy, vitamin B12, and folic acid. Results Serum vitamin B12 and folic acid levels were significantly lower in PPR patients than in the healthy controls (p = 0.011 and p = 0.0173, respectively). Although serum Hcy levels did not significantly differ between PPR patients and healthy controls, PPR severity was positively correlated with serum Hcy levels (p < 0.001). Conclusions Our results suggest a possible association between hyperhomocysteinemia and vitamin B12 deficiency in patients with PPR.
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14
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Paciullo F, Menduno PS, Tucci D, Caricato A, Cagini C, Gresele P. Vitamin B12 levels in patients with retinal vein occlusion and their relation with clinical outcome: a retrospective study. Intern Emerg Med 2022; 17:1065-1071. [PMID: 35028874 DOI: 10.1007/s11739-021-02905-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 11/29/2021] [Indexed: 11/05/2022]
Abstract
Retinal vein occlusion (RVO) is the second most common retinal vascular disorder, after diabetic retinopathy. Most patients suffering RVO develop some degree of visual loss consequent to retinal complications such as edema and microhemorrhages. Even if some risk factors for RVO have been identified, the clinical outcome of RVO remains highly unpredictable because studies investigating potential prognostic markers for visual improvement are lacking. Cyanocobalamin belongs to the group of B vitamins and plays a role in homocysteine metabolism; however, cyanocobalamin deficiency associates with an increase of some toxic bioproducts involved in endothelial injury and platelet activation independent of homocysteine levels. We retrospectively evaluated the levels of vitamin B12 at diagnosis in 203 patients with RVO, and in a parallel cohort of 120 age- and sex-matched patients without RVO from an internal medicine ward, and correlated them with visual outcome at follow-up (median time 150 days, IQR 30-210). In patients with RVO, vitamin B12 levels at diagnosis were significantly lower than in controls and independently predicted worse clinical outcome at multivariate analysis (OR 3.2; CIs 1.2-8.2; p = 0.015). Our data suggest the opportunity to prospectively evaluate the effect on visual outcome of cyanocobalamin supplementation in RVO patients.
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Affiliation(s)
- Francesco Paciullo
- Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Strada Vicinale Via delle Corse, 06126, Perugia, Italy.
- Ospedale di Assisi, via Valentin Muller 1, Assisi, Perugia, Italy.
| | - Paola Santina Menduno
- Division of Ophthalmology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Davide Tucci
- Division of Ophthalmology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Anna Caricato
- Division of Ophthalmology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Carlo Cagini
- Division of Ophthalmology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Paolo Gresele
- Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Strada Vicinale Via delle Corse, 06126, Perugia, Italy
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15
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Celiac Disease and Thrombotic Events: Systematic Review of Published Cases. Nutrients 2022; 14:nu14102162. [PMID: 35631302 PMCID: PMC9144428 DOI: 10.3390/nu14102162] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 02/04/2023] Open
Abstract
Extraintestinal manifestations of celiac disease (CD) should be considered, even in patients without typical intestinal symptoms. The aim of our study is to examine the literature regarding the occurrence of thrombotic events in CD, and to synthesize the data from case reports and case series. A systematic review of the literature was conducted by searching the Pub-Med/MEDLINE database, from the date of database inception to January 2022, to identify published cases and case series on this topic, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 55 cases were included in the study. The majority of patients were previously healthy individuals, with no comorbidities. In less than one-third of the cases (30.91%), the diagnosis of CD was established before the onset of thrombosis, while in the remaining cases (34.54%), thrombosis preceded the diagnosis or was diagnosed concomitantly with CD. The most common sites for thrombosis occurrence were hepatic veins (30.91%), while thrombosis of cerebral blood vessels, deep venous thrombosis of lower extremities, and pulmonary thromboembolism were less frequent. Thrombosis was most commonly isolated to one site only (78.18%). In 69.09% of cases (n = 38), some form of anticoagulation, along with a gluten-free diet, was initiated.
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16
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Goubran H, Ragab G, Sabry W. Metabolism-mediated thrombotic microangiopathy and B12. VITAMINS AND HORMONES 2022; 119:441-455. [PMID: 35337630 DOI: 10.1016/bs.vh.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Thrombotic microangiopathies (TMAs) are a group of life-threatening conditions requiring urgent management and characterized by a clinical triad of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic tissue injury. Severe vitamin B12 (Cobalamin-Cbl) deficiency or defective cobalamin metabolism, particularly defects in intracellular B12 metabolism, may lead to a TMA-like picture. The latter has been termed metabolism-mediated TMA (MM-TMA). This confusing picture is mediated partly by ineffective erythropoiesis with significant red cell fragmentation resulting in a hemolytic pattern, coupled with reduced platelet production and endothelial injury with organ damage resulting from accumulated toxic byproducts of B12 dysmetabolism. However, unlike in classic thrombotic thrombocytopenic purpura, where therapeutic plasma exchange has to be initiated promptly, cases of MM-TMA can be treated, if diagnosed properly, with adequate B12 replacement.
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Affiliation(s)
- Hadi Goubran
- College of Medicine, University of Saskatchewan & Saskatoon Cancer Centre, SK, Canada.
| | - Gaafar Ragab
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Egypt
| | - Waleed Sabry
- College of Medicine, University of Saskatchewan & Saskatoon Cancer Centre, SK, Canada.
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17
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Orolu A, Adeyemo T, Akanmu A. Elevated homocysteine and crises state in patients with sickle cell anemia: A comparative study. JOURNAL OF CLINICAL SCIENCES 2022. [DOI: 10.4103/jcls.jcls_33_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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18
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Lamponi S. Bioactive Natural Compounds with Antiplatelet and Anticoagulant Activity and Their Potential Role in the Treatment of Thrombotic Disorders. Life (Basel) 2021; 11:1095. [PMID: 34685464 PMCID: PMC8540276 DOI: 10.3390/life11101095] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/08/2021] [Accepted: 10/13/2021] [Indexed: 12/19/2022] Open
Abstract
Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants' bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders.
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Affiliation(s)
- Stefania Lamponi
- Department of Biotechnologies, Chemistry and Pharmacy and SienabioACTIVE, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
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19
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Sheraton M, Patel D, Houck R. Point-of-Care Ultrasonography Saves the Day in Dilated Cardiomyopathy: A Rare Presentation of Hyperhomocysteinemia. Cureus 2021; 13:e16699. [PMID: 34336538 PMCID: PMC8319162 DOI: 10.7759/cureus.16699] [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] [Accepted: 07/27/2021] [Indexed: 11/06/2022] Open
Abstract
Here, we report a case of hereditary hyperhomocysteinemia presenting as dilated cardiomyopathy which was successfully diagnosed using a combination of point-of-care ultrasonography (POCUS) and echocardiogram (ECHO). A 39-year-old Caucasian male with a family history of homocystinuria and early deaths in adult male members from cardiovascular disease presented with complaints of purplish discoloration and 4/10 pain in bilateral feet along with severe nausea/vomiting for the last two days. Physical examination was significant for tachycardia, low normal mean arterial pressures, dry mucous membranes, right basilar crepitations, S3 gallop with holosystolic murmur along with peripheral cyanosis, and pitting edema. Laboratory examination revealed leucocytosis, elevated d-dimers, high anion gap metabolic acidosis secondary to worsening renal function, elevated liver enzymes, hyperhomocysteinemia, elevated B-type natriuretic peptide, and troponins along with low protein C and S. Electrocardiogram demonstrated left axis deviation with abnormal QRS-T angle and intraventricular conduction delay with a QRS duration of 133 ms. Bedside POCUS and ECHO revealed marked left ventricular dilatation with an ejection fraction of 10% and mitral regurgitation. Computed tomography angiography of the chest and abdomen was positive for partial left subclavian vein thrombus with extensive collateral formation and right-sided pleural effusion. The patient was started on anticoagulants and promptly transferred to a tertiary care center for left ventricular assist device placement. Hyperhomocysteinemia can present with atypical heart failure symptoms, and early usage of bedside POCUS and interpretation of findings in the context of family history are imperative for a successful diagnosis.
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Affiliation(s)
- Mack Sheraton
- Emergency Medicine, Trinity West Medical Center, Steubenville, USA
| | - Dhaval Patel
- Internal Medicine, Trinity West Medical Center, Steubenville, USA
| | - Richard Houck
- Emergency Medicine, Trinity West Medical Center, Steubenville, USA
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20
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Effects of Hyperhomocysteinemia on the Platelet-Driven Contraction of Blood Clots. Metabolites 2021; 11:metabo11060354. [PMID: 34205914 PMCID: PMC8228611 DOI: 10.3390/metabo11060354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/21/2021] [Accepted: 05/30/2021] [Indexed: 12/17/2022] Open
Abstract
Hyperhomocysteinemia (HHcy) is associated with thrombosis, but the mechanistic links between them are not understood. We studied effects of homocysteine (Hcy) on clot contraction in vitro and in a rat model of HHcy. Incubation of blood with exogenous Hcy for 1 min enhanced clot contraction, while 15-min incubation led to a dose-dependent suppression of contraction. These effects were likely due to direct Hcy-induced platelet activation followed by exhaustion, as revealed by an increase in fibrinogen-binding capacity and P-selectin expression determined by flow cytometry. In the blood of rats with HHcy, clot contraction was enhanced at moderately elevated Hcy levels (10–50 μM), while at higher Hcy levels (>50 μM), the onset of clot contraction was delayed. HHcy was associated with thrombocytosis combined with a reduced erythrocyte count and hypofibrinogenemia. These data suggest that in HHcy, platelets get activated directly and indirectly, leading to enhanced clot contraction that is facilitated by the reduced content and resilience of fibrin and erythrocytes in the clot. The excessive platelet activation can lead to exhaustion and impaired contractility, which makes clots larger and more obstructive. In conclusion, HHcy modulates blood clot contraction, which may comprise an underappreciated pro- or antithrombotic mechanism.
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21
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Tchantchou F, Goodfellow M, Li F, Ramsue L, Miller C, Puche A, Fiskum G. Hyperhomocysteinemia-Induced Oxidative Stress Exacerbates Cortical Traumatic Brain Injury Outcomes in Rats. Cell Mol Neurobiol 2021; 41:487-503. [PMID: 32405706 PMCID: PMC11448695 DOI: 10.1007/s10571-020-00866-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 05/05/2020] [Indexed: 02/07/2023]
Abstract
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among military service members and civilians in the United States. Despite significant advances in the understanding of TBI pathophysiology, several clinical reports indicate that multiple genetic and epigenetic factors can influence outcome. Homocysteine (HCY) is a non-proteinogenic amino acid, the catabolism of which can be dysregulated by stress, lifestyle, aging, or genetic abnormalities leading to hyperhomocysteinemia (HHCY). HHCY is a neurotoxic condition and a risk factor for multiple neurological and cardiovascular disorders that occurs when HCY levels is clinically > 15 µM. Although the deleterious impact of HHCY has been studied in human and animal models of neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease, it has not been addressed in TBI models. This study tested the hypothesis that HHCY has detrimental effects on TBI pathophysiology. Moderate HHCY was induced in adult male Sprague Dawley rats via daily administration of methionine followed by impact-induced traumatic brain injury. In this model, HHCY increased oxidative stress, upregulated expression of proteins that promote blood coagulation, exacerbated TBI-associated blood-brain barrier dysfunction and promoted the infiltration of inflammatory cells into the cortex. We also observed an increase of brain injury-induced lesion size and aggravated anxiety-like behavior. These findings show that moderate HHCY exacerbates TBI outcomes and suggest that HCY catabolic dysregulation may be a significant biological variable that could contribute to TBI pathophysiology heterogeneity.
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Affiliation(s)
- Flaubert Tchantchou
- Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD, 21201, USA.
| | - Molly Goodfellow
- Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD, 21201, USA
| | - Fengying Li
- Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD, 21201, USA
| | - Lyric Ramsue
- Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD, 21201, USA
| | - Catriona Miller
- Aeromedical Research, U.S Air Force School of Aerospace Medicine, Dayton, OH, USA
| | - Adam Puche
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Gary Fiskum
- Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, Baltimore, MD, 21201, USA
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22
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Bernards J, Doubel P, Meeus G, Lerut E, Corveleyn A, Van Den Heuvel LP, Meersseman W, Kuypers DK, Claes KJ. Hyperhomocysteinemia: a trigger for complement-mediated TMA? Acta Clin Belg 2021; 76:65-69. [PMID: 31401947 DOI: 10.1080/17843286.2019.1649039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Kidney biopsy confirmed this diagnosis with histological changes including intimal edema, arteriolar thrombi, and severe tubulointerstitial damage. Fundoscopy showed hypertensive retinopathy stage IV. Subsequent biochemical screening revealed normal complement testing and a marked elevation in homocysteine concentration (161 µmol/L; normal value 7-15 µmol/L). Other secondary causes of TMA were excluded. Further genetic testing for cobalamin C (cblC) deficiency showed no pathogenic mutations in the MMACHC gene. However, a homozygous c.665C>T polymorphism (NM_005957.4) in the methylenetetrahydrofolate reductase (MTHFR) gene was found explaining the severe hyperhomocysteinemia due to reduced activity of MTHFR. Additional genetic testing for alternative complement pathway proteins showed mutations in the genes encoding factor H and factor B, both categorized as possibly pathogenic using mutation prediction software. This is the first described case of TMA in a patient with severe hyperhomocysteinemia caused by a genetic defect other than cblC. We postulate that endothelial damage due to hyperhomocysteinemia and hypertension could have triggered the TMA episode in this patient with two possible predisposing pathogenic mutations in the alternative complement pathway. Furthermore, our case demonstrates the need for complete full diagnostic testing in patients with TMA.
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Affiliation(s)
- J Bernards
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - P Doubel
- Department of Nephrology, AZ Groeninge Hospital, Kortrijk, Belgium
| | - G Meeus
- Department of Nephrology, AZ Groeninge Hospital, Kortrijk, Belgium
| | - E Lerut
- Department of Pathology, University Hospitals Leuven, Leuven
| | - A Corveleyn
- Department of Pediatric Nephrology, Department of Development and Regeneration, University Hospitals Leuven, Leuven, Belgium
| | - L P Van Den Heuvel
- Department of Pediatric Nephrology, Department of Development and Regeneration, University Hospitals Leuven, Leuven, Belgium
- Department of Pediatric Nephrology, Radboud UMC, Nijmegen, The Netherlands
| | - W Meersseman
- Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - D K Kuypers
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium
| | - KJ Claes
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium
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23
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Li J, Ge P, Zhang Q, Lin F, Wang R, Zhang Y, Zhang D, Wang W, Zhao J. Hyperhomocysteinemia is a risk factor for postoperative ischemia in adult patients with moyamoya disease. Neurosurg Rev 2021; 44:2913-2921. [PMID: 33506361 DOI: 10.1007/s10143-021-01482-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/14/2020] [Accepted: 01/21/2021] [Indexed: 12/14/2022]
Abstract
Growing evidence has suggested that hyperhomocysteinemia (HHcy) is a risk factor for cerebral infarction. However, the effect of HHcy on postoperative cerebral ischemia is still unclear. We aim to investigate the relationship between HHcy and postoperative ischemia of adult patients with moyamoya disease (MMD). A total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 14 patients accepting conservative therapy, all 124 patients who underwent surgical treatment were enrolled. Patients were grouped according to postoperative ischemia and HHcy presentation, respectively. Clinical data and laboratory examinations were compared by statistical analyses. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Comparing to the normal, patients with postoperative ischemia were higher in serum homocysteine (Hcy) level (P = 0.039) and HHcy ratio (P = 0.035). Furthermore, HHcy was more common in males (P = 0.007) than females. Logistic analysis results showed that HHcy (OR 5.234, 95% CI 1.127-24.315; P = 0.035) was an independent risk factor. HHcy was significantly associated with postoperative ischemia in MMD patients. Our study found that HHcy was correlated to the risk of postoperative ischemia. HHcy can be used as an indicator and a potential therapeutic target for postoperative ischemia in adult patients with MMD. URL: http://www.chictr.org . Unique identifier: ChiCTR2000031412.
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Affiliation(s)
- Junsheng Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Peicong Ge
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Qian Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Fa Lin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Rong Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Yan Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Dong Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China
| | - Wen Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China. .,China National Clinical Research Center for Neurological Diseases, Beijing, China. .,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China. .,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. .,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China.
| | - Jizong Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nan Si Huan Xi Road 119, Fengtai District, Beijing, 100070, China. .,China National Clinical Research Center for Neurological Diseases, Beijing, China. .,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China. .,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. .,Beijing Translational Engineering Center for 3D Printer in Clinical Neuroscience, Beijing, China. .,Savaid Medical School, University of the Chinese Academy of Sciences, Beijing, China.
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24
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Li B, Li Y, Xu S, Chen H, Dai S, Peng X, Wang L, Liang Y, Li C, Tang B, Zhu L, Zhang T, Lv C, Wang C, Han L. A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population. J Clin Lab Anal 2020; 35:e23689. [PMID: 33382484 PMCID: PMC7957978 DOI: 10.1002/jcla.23689] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Ischemic stroke (IS) is a serious global health burden. In order to improve our understanding of the risk factors associated with IS, we investigated the combined effect of the methylation of five genes related to the metabolism of homocysteine on developing IS. METHODS Quantitative methylation-specific PCR was used to measure the levels of promoter methylation in hypertensive and stroke patients. The cutoff value calculated by the maximum Youden index was used to classify the levels of gene methylation as hypomethylation and hypermethylation. Logistic regression was used to explore the relationship between gene methylation and IS. RESULTS The methylation levels of the genes encoding methylenetetrahydrofolate dehydrogenase 1 [MTHFD1], cystathionine β-synthase [CBS], and dihydrofolate reductase [DHFR] in hypertensive patients were higher than those in stroke patients (all p < 0.01). MTHFD1 hypermethylation, CBS hypermethylation, and DHFR hypermethylation were protective factors for stroke after adjustment for confounding factors. Compared with individuals carrying none of the biomarkers, the ORs [95% CIs] for stroke of those with 1 and 2 elevated biomarkers were 4.068 [1.670-9.913] and 15.345 [6.198-37.994] after adjustment for confounding factors. The participants with a larger number of biomarkers had an increased risk of stroke (p for trend <0.001). For the combination biomarkers, the area under the curve of the receiver operating characteristic was 0.716. CONCLUSION A significant linear relationship between the number of elevated biomarkers and the risk of stroke has been observed, suggesting that elevations of these biomarkers could be used for potentially predicting the disease.
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Affiliation(s)
- Bo Li
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Yuying Li
- Shenzhen Polytechnic, Shenzhen, China
| | - Shan Xu
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Hongen Chen
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Shudong Dai
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Xiaoling Peng
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Li Wang
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Yaping Liang
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Cheng Li
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Biwei Tang
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Liqing Zhu
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Tao Zhang
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Chunfang Lv
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Changyi Wang
- Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Liyuan Han
- Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
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25
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Thomas T, Stefanoni D, Reisz JA, Nemkov T, Bertolone L, Francis RO, Hudson KE, Zimring JC, Hansen KC, Hod EA, Spitalnik SL, D’Alessandro A. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI Insight 2020; 5:140327. [PMID: 32559180 PMCID: PMC7453907 DOI: 10.1172/jci.insight.140327] [Citation(s) in RCA: 391] [Impact Index Per Article: 78.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 06/17/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.
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Affiliation(s)
- Tiffany Thomas
- Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
| | - Davide Stefanoni
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
| | - Julie A. Reisz
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
| | - Travis Nemkov
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
| | - Lorenzo Bertolone
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
| | - Richard O. Francis
- Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
| | - Krystalyn E. Hudson
- Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
| | - James C. Zimring
- Department of Pathology, University of Virginia, Charlottesville, Virginia, USA
| | - Kirk C. Hansen
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
| | - Eldad A. Hod
- Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
| | - Steven L. Spitalnik
- Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
| | - Angelo D’Alessandro
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver – Anschutz Medical Campus, Aurora, Colorado, USA
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26
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Sabry W, Elemary M, Burnouf T, Seghatchian J, Goubran H. Vitamin B12 deficiency and metabolism-mediated thrombotic microangiopathy (MM-TMA). Transfus Apher Sci 2019; 59:102717. [PMID: 31902683 DOI: 10.1016/j.transci.2019.102717] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Thrombotic microangiopathies (TMA) are characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ damage resulting from mechanical factors, accumulation of the ultra-large von Willebrand factor multimers or complement-mediated abnormalities. Severe acquired vitamin B12 (Cobalamin - Cbl) deficiency or congenital defective Cbl metabolism could lead to a picture that mimics TMA. The later has been termed metabolism-mediated TMA (MM- TMA). This confusing picture is mediated partly by the large red cell fragmentation coupled with reduced platelet production in the absence of vitamin B12 and partly by the accumulated byproducts and metabolites that induce endothelial injury and hence organ damage. Expensive and complicated treatment for TMA is often initiated on an empiric basis, pending the results of confirmatory tests. In contrast, vitamin B12 Pseudo-TMA and MM-TMA could be treated with proper vitamin B12 supplementation. It is therefore important to identify these disorders promptly. The recent availability of a validated scoring system such as the PLASMIC score uses simple clinical and laboratory parameters. As it incorporates the mean corpuscular volume in its laboratory parameters, this helps in the identification of pseudo and MM-TMA. Perhaps some minor modification of this scoring system by changing the parameters of hemolysis to include reticulocytosis and rather than and/or other hemolytic parameters could even help refine this identification.
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Affiliation(s)
- Waleed Sabry
- Saskatoon Cancer Centre and College of Medicine, University of Saskatchewan, Saskatoon, Canada
| | - Mohamed Elemary
- Saskatoon Cancer Centre and College of Medicine, University of Saskatchewan, Saskatoon, Canada
| | - Thierry Burnouf
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, International PhD Program in Biomedical Engineering, College of Biomedical Engineering, and Research Center of Biomedical Devices, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
| | - Jerard Seghatchian
- International Consultancy in Blood Components Quality/Safety Improvement, Audit/Inspection and DDR Strategies, London, UK
| | - Hadi Goubran
- Saskatoon Cancer Centre and College of Medicine, University of Saskatchewan, Saskatoon, Canada.
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27
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Malkani RH, Karia R, Thadani S. A Study of Risk Factors of Chronic Venous Insufficiency and its Association with Features Suggestive of Preceding or Present Deep Venous Thrombosis. Indian J Dermatol 2019; 64:366-371. [PMID: 31543530 PMCID: PMC6749769 DOI: 10.4103/ijd.ijd_271_18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background: Deep venous thrombosis (DVT), even though resolved, may damage the valves and may lead to chronic venous insufficiency (CVI). We designed the present study to examine the thrombotic markers or other ultrasound features in the absence of active thrombosis in patients presenting with features suggestive of CVI. Materials and Methods: It was a cross-sectional study of 50 DVT patients. We collected a detailed history of presenting symptoms (onset, progression, and duration) and associated history of aggravating factors. After classifying the patients, color Doppler investigation for DVT and venous incompetence and blood investigations such as Factor V, D-Dimer, total cholesterol, total triglycerides, homocysteine, high-density lipoproteins, low-density lipoproteins (LDL), and very LDL were done. Results: We found a raised Factor V significantly more in patients classified as severe under clinical classification compared with nonsevere (19% and 0%; P = 0.05) and in patients with a high Venous Severity Clinical Score (VSCS) compared to those with a low VSCS score (17% and 0%; P = 0.03). We also found that perforators were significantly more in patients with a high VSCS score (88% and 58%; P = 0.02), in patients with a primary venous etiology compared with those without any venous etiology (97% and 1%; P < 0.0001), in patients with obstruction/reflux compared to those without any pathology (95% and 0%; P < 0.0001), and in patients with severe clinical classification compared with nonsevere patient (95% and 55%; P = 0.002). Conclusions: Clinical or subclinical DVT, an important cause of CVI, may not always be seen on ultrasound, especially after resolution. However, they may have the presence of blood parameters (Factor V and hyperhomocysteinemia) suggestive of DVT; these can be used as proxy markers for the current or previous DVT.
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Affiliation(s)
- Ram H Malkani
- Department of Dermatology, Jaslok Hospital, Mumbai, Maharashtra, India
| | - Rusina Karia
- Department of Dermatology, Jaslok Hospital, Mumbai, Maharashtra, India
| | - Sneh Thadani
- Department of Dermatology, Jaslok Hospital, Mumbai, Maharashtra, India
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28
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Combined Oral Contraceptive Effects on Low-Grade Chronic Inflammatory Mediators in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Int J Inflam 2018; 2018:9591509. [PMID: 30595838 PMCID: PMC6286752 DOI: 10.1155/2018/9591509] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/04/2018] [Indexed: 02/03/2023] Open
Abstract
Polycystic ovary syndrome is associated with dyslipidemia, dysglycemia, metabolic syndrome, and low-grade chronic inflammation, which increase the risks for cardiovascular disease. Combined oral contraceptives may affect the mediators of low-grade chronic inflammation with potential additive risk in PCOS patients. This meta-analysis investigates the impact of oral contraceptive on markers of chronic inflammation in PCOS patients. Pubmed, Scopus, and Cochrane database were used to search studies reporting on this matter in the target population. Twenty seven studies were selected, including a total of 838 women. The data were expressed as the standardized mean difference. The random-effects model was used to summarize effect sizes. Heterogeneity was examined using Cochran's test (Q) and I2 statistics. Most of the preparations increased C-reactive protein (CRP) in PCOS patients (p >0.001). The increase in homocysteine levels was not significant (p >0.05). Follistatin significantly increased with pills containing cyproterone acetate (p= 0.008). Interleukin-6 changes were inconsistent and plasminogen activator inhibitor-1 decreased with pills containing desogestrel, norgestimate, and drospirenone. Collectively, the results of this review indicate that oral contraceptives modify most inflammatory markers of PCOS patients. However, the clinical implications are not clear yet and future studies must consider longer follow-up and the inclusion of objective clinical parameters.
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29
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Andreenko EY, Yavelov IS, Loukianov ММ, Vernohaeva AN, Drapkina OM, Boytsov SA. Ischemic Heart Disease in Subjects of Young Age: Current State of the Problem. Features of Etiology, Clinical Manifestation and Prognosis. ACTA ACUST UNITED AC 2018; 58:24-34. [PMID: 30625075 DOI: 10.18087/cardio.2018.11.10195] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 11/24/2018] [Indexed: 11/18/2022]
Abstract
In addition to conventional risk factors in young patients with ischemic heart disease (IHD) numerous other risk factors including genetics play an important role in its causation. Molecular genetic testing is recommended for the detection of monogenic diseases with a high risk of developing IHD, such as familial hypercholesterolemia. In majority ofyoung patients, the first manifestation of IHD is an acute coronary syndrome. Young patients with IHD more often have normal coronary arteries or single-vessel coronary disease, and in up to 20% of them cause of myocardial ischemia is not related to atherosclerosis. In general, young patients with IHD have better prognosis. However, there are sex differences in IHD outcomes the prognosis of patients with premature IHD and reason for this is still unclear.
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Affiliation(s)
- E Yu Andreenko
- National Medical Research Center for Preventive Medicine.
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30
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Abstract
In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed. The MLR model explained 64% variability in homocysteine, while the neurofuzzy model showed higher accuracy in predicting homocysteine with a mean absolute error of 0.00002 μmol/L. Methylene tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and 5- methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) A66G were shown to be positively associatiated with homocysteine, while nonvegetarian diet, serine hydroxymethyltransferase 1 (SHMT1) C1420T and TYMS 5'-UTR 28 bp tandem repeat exhibited negative association with homocysteine. The protective role of SHMT1 C1420T was attributed to more H-bonding interactions in the mutant modelled compared to the wild type, as shown through in silico analysis. To conclude, polymorphisms in genes regulating remethylation of homocysteine strongly influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp tandem repeat or nonvegetarian diet can lower homocysteine levels.
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31
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Weitz IC. Thrombotic microangiopathy in cancer. Thromb Res 2018; 164 Suppl 1:S103-S105. [PMID: 29703465 DOI: 10.1016/j.thromres.2018.01.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/08/2018] [Indexed: 12/28/2022]
Abstract
Thrombotic microangiopathy (TMA) is clinical syndrome based on the presence of thrombocytopenia (platelet count <150 K or a reduction of the platelet count by >30% from baseline) accompanied by fragmentation hemolysis (MAHA) and evidence of organ damage. It can be seen in a variety of disorders including thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS), shigatoxin related hemolytic uremic syndrome (STEC-HUS). Cancer itself has long been associated with both macro and microvascular thrombosis. In addition, treatment with chemotherapy as well as hematopoetic stem cell transplantation (HCST) has been associated with atypical hemolytic uremic (aHUS) like syndrome. In this review, I will discuss the pathophysiology of TMA in cancer, chemotherapy associated HUS, and HSCT, well as new therapeutic interventions.
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Affiliation(s)
- Ilene Ceil Weitz
- Jane Anne Nohl Division of Hematology, Department of Medicine, University of Southern California-Keck School of Medicine, Los Angeles, CA, USA.
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32
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Zhou F, Zhou L, Guo T, Wang N, Hao H, Zhou Y, Yu D. Plasma proteomics reveals coagulation, inflammation, and metabolic shifts in H-type hypertension patients with and without acute ischemic stroke. Oncotarget 2017; 8:100384-100395. [PMID: 29245986 PMCID: PMC5725028 DOI: 10.18632/oncotarget.22233] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 10/03/2017] [Indexed: 12/26/2022] Open
Abstract
Systematic profiling of a larger portion of circulating plasma proteome provide opportunities for unbiased discovery of novel markers to improve diagnostic, therapeutic, or predictive accuracy. This study aimed to identify differentially expressed proteins (DEPs) in plasma that could provide overall insight into the molecular changes of both H- type hypertension (HH) and HH-related acute ischemic stroke (AIS). This study used an iTRAQ-based LC-MS/MS proteomics approach to screen for plasma DEPs in HH patients with and without AIS, and controls. After excluding highly abundant plasma proteins, more than 600 proteins, and their relative levels, were identified. Of these, 26 DEPs, each showing > 1.2-fold change, were identified in HH and HH-related AIS patients compared with controls. Bioinformatics analysis revealed that these DEPs were enriched in 21 functional gene ontology items; “blood coagulation” was the most predominant pathway showing enrichment. Of these, eight DEPs were located in the hub position of networks involved with protein-protein interactions. AT-3, CRP, ApoB, and AHSG were further validated in each group by enzyme-linked immune sorbent assays. Comparing HH-related AIS with HH, the areas under the curve for AT-3, CRP, ApoB, and AHSG were 0.698, 0.892, 0.626, and 0.847, respectively. This proteomic profiling study provided enhanced pathophysiological understanding of the regulatory processes involved in coagulation, inflammation, and metabolism, and identified a panel of novel biomarkers for detecting HH-related AIS during its pre-stroke stage.
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Affiliation(s)
- Feng Zhou
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Lv Zhou
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Tie Guo
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Nianzhen Wang
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Haizhen Hao
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Yanhui Zhou
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
| | - Dan Yu
- Department of Neurology, Affiliated Haikou Hospital at Xiangya Medical School of Central South University, Haikou 570208, Hainan, China
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33
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Kottke-Marchant K. Diagnostic approach to microangiopathic hemolytic disorders. Int J Lab Hematol 2017; 39 Suppl 1:69-75. [DOI: 10.1111/ijlh.12671] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Accepted: 03/03/2017] [Indexed: 01/29/2023]
Affiliation(s)
- K. Kottke-Marchant
- Medical Director Hemostasis and Thrombosis Robert J; Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic; 9500 Euclid Avenue LL3-1 Cleveland, OH 44195
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Abstract
Venous thromboembolism, usually entailing deep vein thrombosis, pulmonary embolism, or both, is a complex and multifactorial disorder, in which a number of putative conditions interplay and finally contribute to propel the individual risk over a certain degree, so ultimately culminating in the development of venous occlusive disorders. Thrombophilia is commonly defined as a propensity to develop venous thromboembolism on the basis of an underlying hypercoagulable state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis. The thrombophilic conditions are conventionally classified as inherited (or genetically determined) and acquired. The former include deficiencies of natural anticoagulants such as antithrombin, protein C, protein S, increased values of clotting factors (especially factor VIII), as well as prothrombotic polymorphisms in genes encoding for factor V (i.e., factor V Leiden) and prothrombin. The latter conditions mainly entail antiphospholipid antibody syndrome, malignancy, acquired elevations of coagulation factors or acquired reduction of natural inhibitors, or hyperhomocysteinemia. Deepened knowledge of all potential risk factors, as well as the clear understanding of their role in the pathophysiology of venous thrombosis, are both essential to help achieve a faster and more efficient diagnosis of this condition as well as a more effective prophylaxis of patients at higher risk and treatment of those with manifest disease.
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Affiliation(s)
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Elisa Danese
- Section of Clinical Biochemistry, University of Verona, Verona, Italy
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Friso S, Udali S, De Santis D, Choi SW. One-carbon metabolism and epigenetics. Mol Aspects Med 2016; 54:28-36. [PMID: 27876555 DOI: 10.1016/j.mam.2016.11.007] [Citation(s) in RCA: 144] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 11/18/2016] [Indexed: 12/11/2022]
Abstract
The function of one-carbon metabolism is that of regulating the provision of methyl groups for biological methylation reactions including that of DNA and histone proteins. Methylation at specific sites into the DNA sequence and at histone tails are among the major epigenetic feature of mammalian genome for the regulation of gene expression. The enzymes within one-carbon metabolism are dependent from a number of vitamins or nutrients that serve either as co-factors or methyl acceptors or donors among which folate, vitamin B12, vitamin B6, betaine, choline and methionine have a major role. Several evidences show that there is a strict inter-relationship between one-carbon metabolism nutrients and epigenetic phenomena. Epigenetics is closely involved in gene transcriptional regulation through modifications super-imposed to the nucleotide sequence of DNA, such as DNA methylation, through chromatin remodeling systems that involves post-translational modifications of histones or through non-coding RNAs-based mechanisms. The epigenetic features of the genome are potentially modifiable by the action of several environmental factors among which nutrients cover a special place and interest considering their potential of influencing regulatory pathways at a molecular level by specific nutritional intervention and eventually influence disease prevention and outcomes. The present review will focus on the link between one-carbon nutrients and epigenetic phenomena based on the current knowledge from findings in cell culture, animal models and human studies.
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Affiliation(s)
- Simonetta Friso
- Department of Medicine, University of Verona School of Medicine, Verona, Italy.
| | - Silvia Udali
- Department of Medicine, University of Verona School of Medicine, Verona, Italy
| | - Domenica De Santis
- Department of Medicine, University of Verona School of Medicine, Verona, Italy
| | - Sang-Woon Choi
- Tufts University School of Nutrition Science and Policy, Boston, MA, USA; Chaum Life Center, CHA University, Seoul, South Korea
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Bochenek ML, Schütz E, Schäfer K. Endothelial cell senescence and thrombosis: Ageing clots. Thromb Res 2016; 147:36-45. [DOI: 10.1016/j.thromres.2016.09.019] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 09/16/2016] [Accepted: 09/17/2016] [Indexed: 01/28/2023]
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Mukherjee AK, Manna SK, Roy SK, Chakraborty M, Das S, Naskar JP. Plasma-aminothiols status and inverse correlation of total homocysteine with B-vitamins in arsenic exposed population of West Bengal, India. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART A, TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING 2016; 51:962-973. [PMID: 27336853 DOI: 10.1080/10934529.2016.1191816] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Chronic arsenic toxicity is a serious environmental health problem across the world. Bangladesh and India (particularly the state of West Bengal) are the worst affected countries with such problem. The present study reports plasma-aminothiols (p-aminothiols) like L-cysteine (L-Cys), cysteinyl glycine (Cys-gly), total homocysteine (t-Hcy) and glutathione (GSH) status, and the inverse relationship of t-Hcy with B-vitamins (B1, B6, B9 and B12) in arsenic exposed population of West Bengal, India. Reverse phase HPLC was used to measure p-aminothiols and serum B-vitamins in different arsenic exposed population. Arsenic in drinking water and urine were measured by flow injection analysis system - Atomic Absorption Spectrometry (FIAS-AAS) and Transversely heated graphite atomizer (THGA-AAS) techniques, respectively. Water arsenic exposure was >50 µg/L in 50% population, of which majority (33.58%) belong to the range of >50-500 µg/L and more than 8% were even >1000 µg/L. Urine arsenic (µg/g creatinine) levels increased with arsenic exposure. The variability among p-aminothiols was also observed with higher exposure to arsenic in drinking water. A significant difference between exposed and control population was noticed for plasma L-Cys. The difference of B-vitamins between the population exposed to <50 and >50 µg/L arsenic in drinking water was also found to be significant. B9 and B12 deficiency with increased consumption of arsenic in water corroborates the anemic conditions commonly observed among arsenic exposed population. The aminothiol status indicated oxidative stress in exposed population. This study demonstrated progressive increase in plasma t-Hcy as well as inverse relationships of serum B-vitamins with increased water arsenic concentration.
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Affiliation(s)
- Ashit K Mukherjee
- a Regional Occupational Health Centre (Eastern), Indian Council of Medical Research, Kolkata , India
| | - Sujoy K Manna
- a Regional Occupational Health Centre (Eastern), Indian Council of Medical Research, Kolkata , India
| | - Sanjit K Roy
- a Regional Occupational Health Centre (Eastern), Indian Council of Medical Research, Kolkata , India
| | - Manisha Chakraborty
- a Regional Occupational Health Centre (Eastern), Indian Council of Medical Research, Kolkata , India
| | - Surajit Das
- a Regional Occupational Health Centre (Eastern), Indian Council of Medical Research, Kolkata , India
| | - Jnan P Naskar
- b Department of Chemistry , Jadavpur University , Kolkata , India
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Tsiara S, Elisaf M, Jagroop IA, Mikhailidis DP. Platelets as Predictors of Vascular Risk: Is There a Practical Index of Platelet Activity? Clin Appl Thromb Hemost 2016; 9:177-90. [PMID: 14507105 DOI: 10.1177/107602960300900301] [Citation(s) in RCA: 217] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Activated platelets play a role in the pathogenesis of coronary heart disease (CHD). Following activation, platelets change shape, aggregate, and release several bioactive substances. The aim of this review is to identify if there is a simple and cost-effective method that indicates platelet activation and predicts the risk of CHD and vascular events. The rationale for identifying high-risk patients is to reduce their risk of vascular events by administering appropriate and effective antiplatelet treatment, like aspirin, clopidogrel, or combination regimens. Many laboratory tests estimating platelet activity have been described. Some are relatively simple, such as spontaneous or agonist-induced platelet aggregation. Other tests include measuring the mean platelet volume (MPV) or plasma soluble P-selectin levels. Some more complex tests include flow cytometry to determine platelet GP Ilb/Illa receptors, platelet surface P-selectin, plateletmonocyte aggregates, and microparticles. Only few prospective studies assessed the predictive value of platelet activation in healthy individuals. Although the MPV seems an 'easy method, there are insufficient data supporting its ability to predict the risk of a vascular event in healthy adults. Platelet aggregation, in whole blood or in platelet-rich plasma was not consistently predictive of vascular risk. Soluble P-selectin measurement is a promising method but it needs further evaluation. Flow cytometry methods are costly, time-consuming, and need specialized equipment. Thus, they are unlikely to be useful in estimating the risk in large numbers of patients. There is as yet no ideal test for the detection of platelet activation. Each currently available test has merits and disadvantages. Simple methods such as the MPV and the determination of platelet release products need further evaluation.
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Affiliation(s)
- Stavroula Tsiara
- Department Clinical Biochemistry, Royal Free University College School of Medicine, University of London, Royal Free Campus, London NW3 2QG, UK
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Li J, Liu Y, Wang T, Zhao L, Feng W. Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis. Climacteric 2016; 19:440-7. [PMID: 27338295 DOI: 10.1080/13697137.2016.1194388] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE To perform a meta-analysis examining the effects of genistein on homocysteine and lipid levels in postmenopausal women. METHODS We systematically searched the PubMed, MEDLINE, and Cochrane Library databases and the ClinicalTrials.gov website for studies. We performed a meta-analysis using weighted mean differences (WMD) and 95% confidence intervals in a random-effects model. We assessed between-study heterogeneity using the Cochran's Q and I(2) statistics. RESULTS Eight randomized, controlled trials with a total of 476 subjects were included in the meta-analysis. Compared with placebos, genistein was effective in reducing plasma levels of homocysteine (WMD, -0.58 μmol/l; p = 0.001), and increasing high density lipoprotein (HDL) cholesterol levels (WMD, 4.9 mg/dl; p = 0.0002). Subgroup analyses revealed that genistein significantly decreased the levels of low density lipoprotein (LDL) cholesterol (WMD, -16.90 mg/dl; p = 0.01), total cholesterol (WMD, -15.83 mg/dl; p = 0.008), and triglycerides (WMD, -46.58 mg/dl; p = 0.03) in postmenopausal women with metabolic syndrome, but had no significant effects in those with no metabolic syndrome. CONCLUSIONS Our meta-analysis demonstrates that genistein significantly reduces homocysteine levels and increases HDL cholesterol levels in postmenopausal women. Genistein also significantly decreases LDL cholesterol, total cholesterol and triglyceride levels in postmenopausal women with metabolic syndrome.
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Affiliation(s)
- J Li
- a Department of Pharmacy , Peking University People's Hospital , Beijing , China ;,b Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences , Peking University Health Science Center , Beijing , China
| | - Y Liu
- a Department of Pharmacy , Peking University People's Hospital , Beijing , China ;,b Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences , Peking University Health Science Center , Beijing , China
| | - T Wang
- b Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences , Peking University Health Science Center , Beijing , China
| | - L Zhao
- c Department of Pharmacy , Beijing Children's Hospital, Capital Medical University , Beijing , China
| | - W Feng
- a Department of Pharmacy , Peking University People's Hospital , Beijing , China
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Abstract
Platelets play an important, but often under-recognized role in cardiovascular disease. For example, the normal response of the platelet can be altered, either by increased pro-aggregatory stimuli or by diminished anti-aggregatory substances to produce conditions of increased platelet activation/aggregation and occur in active cardiovascular disease states both on a chronic (e.g. stable angina pectoris) and acute basis (e.g. acute myocardial infarction). In addition, platelet hyperaggregability is also associated with the risk factors for coronary artery disease (e.g. smoking, hypertension, and hypercholesterolaemia). Finally, the utility of an increasing range of anti-platelet therapies in the management of the above disease states further emphasizes the pivotal role platelets play in the pathogenesis of cardiovascular disease. This paper provides a comprehensive overview of the normal physiologic role of platelets in maintain homeostasis, the pathophysiologic processes that contribute to platelet dysfunction in cardiovascular disease and the associated role and benefits of anti-platelet therapies.
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Affiliation(s)
- Scott Willoughby
- Cardiology Unit, The Queen Elizabeth Hospital, Adelaide University, Adelaide, South Australia, Australia
| | - Andrew Holmes
- Cardiology Unit, The Queen Elizabeth Hospital, Adelaide University, Adelaide, South Australia, Australia
| | - Joseph Loscalzo
- The Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, MA, USA
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Han TW, Zhou SS, Li JT, Tian F, Mu Y, Jing J, Han YF, Chen YD. Homocysteine is associated with the progression of non-culprit coronary lesions in elderly acute coronary syndrome patients after percutaneous coronary intervention. J Geriatr Cardiol 2016; 13:299-305. [PMID: 27403138 PMCID: PMC4921541 DOI: 10.11909/j.issn.1671-5411.2016.04.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Revised: 02/26/2016] [Accepted: 02/27/2016] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND The influence of homocysteine (Hcy) on the migration and proliferation of vascular smooth muscle cells has been well established. However, the impact of Hcy levels on the progression of non-culprit coronary lesions (NCCLs) is controversial. This study aims to evaluate whether the plasma level of Hcy is related to the progression of NCCLs after percutaneous coronary stent implantation in elderly patients with acute coronary syndrome (ACS). METHODS A total of 223 elderly patients (≥ 65 years old) with ACS undergoing stent implantation and follow-up coronary angiography were enrolled. Laboratory determination comprised of blood sample evaluation for Hcy was carried out before baseline coronary intervention. The patients were classified into two groups according to the blood Hcy tertiles (≥ 15 mmol/L or < 15 mmol/L). Patients were followed up for 12.2 months. NCCL progression was assessed by three-dimensional quantitative coronary angiography. RESULTS A significantly higher ratio of NCCL progression was observed in the group with baseline Hcy concentrations above 15 mmol/L compared to the group with concentrations below 15 mmol/L (41/127, 32.3% vs. 14/96, 14.6%, P = 0.002). Multivariate Cox regression analysis showed that Hcy and diabetes mellitus were independent risk factors for NCCL progression. The crude hazard ratio (HR) of NCCL progression for Hcy level was 1.056 (95% CI: 1.01-1.104, P = 0.015). The adjusted HR of NCCL progression for Hcy level was 1.024 (95% CI: 1.007-1.042, P = 0.007). The adjusted HR of NCCL progression for diabetes mellitus was 1.992 (95% CI: 1.15-3.44, P = 0.013). CONCLUSIONS Hcy is an independent risk factor for NCCL progression after 12 months of follow-up in elderly patients with ACS who has undergone percutaneous coronary stenting.
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Affiliation(s)
- Tian-Wen Han
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Shan-Shan Zhou
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Jian-Tao Li
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Feng Tian
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Yang Mu
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Jing Jing
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Yun-Feng Han
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
| | - Yun-Dai Chen
- Department of Cardiology, Chinese PLA General Hospital, Beijing, China
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Wang C, Han L, Wu Q, Zhuo R, Liu K, Zhao J, Zhang L, Hao Y, Fan R, Liu Y, Li R, Chen Z, Zhang T, Chen S, Ma J, Liu S, Peng X, Duan S. Association between homocysteine and incidence of ischemic stroke in subjects with essential hypertension: a matched case-control study. Clin Exp Hypertens 2015; 37:557-62. [PMID: 25992490 DOI: 10.3109/10641963.2015.1026039] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND To assess the association between total plasma homocysteine (tHcy) and ischemic stroke (IS) in hypertensive subjects in a matched case-control study. METHODS This is a 1:2 matched and population-based case-control study, all of the participants were recruited from the 60 communities in Shenzhen, China. Demographic and socioeconomic characteristics, medical records, lifestyle risk factors and other clinical characteristics were obtained from all of the subjects. The association between tHcy and incidence of IS was analyzed by using conditional logistic regression models. RESULTS The median values of plasma tHcy were significantly higher in IS subjects than in non-IS subjects, especially in women. After adjusted for the confounding factors in Model 2, compared with the lowest quartile of tHcy, the odds ratios (ORs) and 95% CIs of the highest quartile of tHcy for IS were 0.83 (0.36-1.90) in men, 4.51 (1.29-15.7) in women and 1.31 (0.70-2.47) in the total subjects; the ORs and 95% CIs for IS per 5 μmol/L increase in homocysteine were 1.11 (0.99-1.22), 1.25 (1.03-1.58) and 1.15 (1.01-1.28) in men, women and total subjects, respectively. We observed significant associations in crude model, Model 1 and Model 2 in women for the comparison of tHcy ≥ 15 μmol/L versus < 15 μmol/L. Interaction analysis showed that the association of tHcy with IS was significant in women (p-interaction = 0.04). CONCLUSION This matched case-control study indicates that tHcy may increase the susceptibility to IS in essential hypertension subjects, especially in women. Further large prospective cohort studies are needed to confirm our findings.
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Affiliation(s)
- Changyi Wang
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Liyuan Han
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Qunhong Wu
- c Department of Social Medicine , School of Public Health, Harbin Medical University , Harbin , Heilongjiang Province , People's Republic of China , and
| | - Renjie Zhuo
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Kui Liu
- d Department of Science Research and Information Management , Zhejiang Provincial Center for Disease Control and Prevention , Hangzhou , China
| | - Jinshun Zhao
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Lina Zhang
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Yanhua Hao
- c Department of Social Medicine , School of Public Health, Harbin Medical University , Harbin , Heilongjiang Province , People's Republic of China , and
| | - Rui Fan
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Yanfen Liu
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Runhua Li
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
| | - Zhongwei Chen
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Tao Zhang
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Sihan Chen
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Jianping Ma
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Shengyuan Liu
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Xiaolin Peng
- a Department of Chronic Disease Prevention and Control , Shenzhen Nanshan Center for Chronic Disease Control , Shenzhen , People's Republic of China
| | - Shiwei Duan
- b Department of Preventive Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University , Ningbo , People's Republic of China
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Zhang M, Wen J, Wang X, Xiao C. High‑dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels. Mol Med Rep 2014; 10:1609-13. [PMID: 24939255 DOI: 10.3892/mmr.2014.2332] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 04/08/2014] [Indexed: 11/05/2022] Open
Abstract
The aim of this study was to investigate the effect of folic acid (FA) on tetrahydrobiopterin (BH4), neopterin, nitric oxide (NO) and homocysteine (Hcy) levels in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro in the presence or absence of Hcy. The effect of various doses of FA on Hcy, BH4, neopterin and NO concentrations in HUVECs was then assessed. In the 5 and 10 nmol/l FA treatment groups, FA was found to significantly increase the levels of BH4 (10.56±3.86 and 11.23±2.1919 pmol/g vs 6.32+2.87 nmol/g; P<0.05 vs. control) and NO production (37.86±12.34 nmol/l, 38.45±11.23 nmol/l vs 26.21±9.24 nmol/l; P<0.001 vs. paired Hcy group), but reduce the levels of Hcy (132.87±29.67 and 140.87±26.76 nmol/l vs. 165.23±30.56 nmol/l; P<0.05 vs. Hcy group). No significant differences were observed in neopterin levels among the different groups of HUVECs. In conclusion, high doses of FA may be capable of protecting endothelial cells through reducing levels of Hcy and increasing BH4 and NO production.
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Affiliation(s)
- Min Zhang
- Department of Cardiovascular Medicine, The Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong 516002, P.R. China
| | - Jinlin Wen
- Department of Cardiovascular Medicine, The Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong 516002, P.R. China
| | - Xiangjiang Wang
- Department of Cardiovascular Medicine, The Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong 516002, P.R. China
| | - Chun Xiao
- Department of Cardiovascular Medicine, The Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong 516002, P.R. China
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Abstract
This review article covers the diverse pathophysiological pathways that can lead to microangiopathic hemolytic anemia and a procoagulant state with or without damage to the kidneys and other organs.
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Affiliation(s)
- James N George
- From the Department of Biostatistics and Epidemiology, College of Public Health, and the Department of Internal Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City (J.N.G.); and the Stead Family Department of Pediatrics and Department of Internal Medicine, University of Iowa, Iowa City (C.M.N.)
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Shu J, Yin S, Tan AZ, He M. Association between the methylenetetrahydrofolate reductase gene C677T polymorphism and sudden sensorineural hearing loss: a meta-analysis. Eur Arch Otorhinolaryngol 2014; 272:2267-74. [DOI: 10.1007/s00405-014-3198-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 07/04/2014] [Indexed: 01/16/2023]
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Luo H, Liu B, Hu J, Wang X, Zhan S, Kong W. Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in cervical artery dissection: a meta-analysis. Cerebrovasc Dis 2014; 37:313-22. [PMID: 24903192 DOI: 10.1159/000360753] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2013] [Accepted: 02/18/2014] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Cervical artery dissection (CAD) is a recognized cause of ischemic stroke. Hyperhomocysteinemia (HHcy), i.e. an elevated concentration of plasma homocysteine, is identified as an independent risk factor for stroke prevalence. However, an association between HHcy and CAD has so far remained unknown. METHODS A meta-analysis was performed to analyze the association between HHcy and CAD as well as the relevance of the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the key enzyme in homocysteine metabolism during CAD. We searched PubMed and Embase for studies reporting homocysteine concentrations or MTHFR genotype frequencies in CAD patients from 1990 to 2013. Outcomes were extracted from studies meeting the inclusion criteria and were subjected to a meta-analysis by the random-effect model. Heterogeneity was assessed by the I(2) test. RESULTS Eight case-control studies with 2,146 individuals fulfilled the required criteria and were included in the meta-analysis. HHcy was found to be significantly associated with CAD (pooled standardized mean difference: 0.96; 95% confidence interval, CI: 0.42-1.49; p < 0.01). We also found a significantly increased risk of CAD in individuals with the MTHFR C677T polymorphism by both the recessive model (TT vs. CT+CC; odds ratio, OR = 1.81; 95% CI: 1.22-2.67; p = 0.003) and the dominant model (TT+CT vs. CC; OR = 1.47; 95% CI: 1.08-1.99; p = 0.014). CONCLUSION Our data suggest positive correlations between HHcy and CAD and between the C677T polymorphism of MTHFR and CAD.
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Affiliation(s)
- Hongzhi Luo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, PR China
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Zhang H, Chen X, Liu L, Fan L, Cao J, Li X, Hu G, Hu Y, Zhu B, Liu X, Gao Y, Ma C, Leng W. High prevalence of aspirin resistance in elderly patients with cardiovascular disease (CVD) and hyperhomocysteinaemia. Arch Gerontol Geriatr 2014; 59:491-5. [PMID: 24880196 DOI: 10.1016/j.archger.2014.04.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Revised: 04/16/2014] [Accepted: 04/24/2014] [Indexed: 11/29/2022]
Abstract
Although aspirin resistance is well reported in CVD, little is known about aspirin response in elderly patients with hyperhomocysteinaemia. The aim of the present study was to explore the prevalence of aspirin resistance in elderly patients with CVD and hyperhomocysteinaemia. A total of 370 elderly patients with CVD were recruited. The study included 216 patients with hyperhomocysteinaemia and 154 patients with normohomocysteinaemia receiving daily aspirin therapy (≥ 75 mg) over 1 month. The effect of aspirin was assessed using by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥ 20% arachidonic acid induced aggregation according to LTA. Aspirin resistance was defined in 48 (13.0%) of 370 patients. The prevalence of aspirin resistance was higher in hyperhomocysteinaemic patients than normohomocysteinaemic patients (16.7% vs. 7.8%, odds ratio (OR)=2.367; 95% confidence interval (CI)=1.188-4.715, p=0.012). In the multivariate logistic regression analysis, hyperhomocysteinaemia (OR=2.406, 95% CI=1.201-4.820, p=0.013) was a significant risk factor for aspirin resistance. A significant number of CVD patients with hyperhomocysteinemia are resistant to aspirin therapy. Hyperhomocysteinemia is a significant risk factor for aspirin resistance in elderly patients with CVD.
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Affiliation(s)
- Huaxin Zhang
- Department of Clinical Laboratory of South Building, Chinese PLA General Hospital, Beijing, China
| | - Xiuying Chen
- Pharmacy Department, Hospital of Chinese Peoples Armed Police Forces, Beijing 100039, PR China
| | - Lin Liu
- Department of Respiratory Disease of South Building, Chinese PLA General Hospital, Beijing, China
| | - Li Fan
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China.
| | - Jian Cao
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China.
| | - Xiaoli Li
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Guoliang Hu
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Yixin Hu
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Bingpo Zhu
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Xianfeng Liu
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Yan Gao
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Cong Ma
- First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
| | - Wenxiu Leng
- Second Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China
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Yang X, Zhou Y, Liu C, Gao X, Wang A, Guo Y, Li W, Zhao X, Liang W. Homocysteine and carotid plaque stability: a cross-sectional study in Chinese adults. PLoS One 2014; 9:e94935. [PMID: 24736609 PMCID: PMC3988131 DOI: 10.1371/journal.pone.0094935] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 03/21/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND PURPOSE This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability. METHODS A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors. RESULTS The mean level of plasma homocysteine in the subjects was 14.9 µmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09-1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17-1.70), but not in women. CONCLUSION The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults.
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Affiliation(s)
- Xin Yang
- Department of General Practice, School of General Practice and Continuing Education, Capital Medical University, Beijing, China
| | - Yong Zhou
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Chao Liu
- Department of Neurosurgery, the Second Hospital of Jilin University, Changchun, China
| | - Xiang Gao
- Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Nutrition, Harvard University School of Public Health, Boston, Massachusetts, United States of America
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuming Guo
- Department of Epidemiology and Biostatistics, University of Queensland School of Population Health, Brisbane, Queensland, Australia
| | - Wen Li
- Department of Ultrasound, Kailuan Hospital, Hebei United University, Tangshan, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wannian Liang
- Department of General Practice, School of General Practice and Continuing Education, Capital Medical University, Beijing, China
- National Health and Family Planning Commission of People’s Republic of China, Beijing, China
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Zhang MJ, Li JC, Yin YW, Li BH, Liu Y, Liao SQ, Gao CY, Zhang LL. Association of MTHFR C677T polymorphism and risk of cerebrovascular disease in Chinese population: an updated meta-analysis. J Neurol 2014; 261:925-35. [DOI: 10.1007/s00415-014-7300-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 02/21/2014] [Accepted: 02/22/2014] [Indexed: 01/22/2023]
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Nienaber-Rousseau C. Dietary strategies to treat hyperhomocysteinaemia based on the biochemistry of homocysteine: a review. SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION 2014. [DOI: 10.1080/16070658.2014.11734495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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