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Kulecki M, Naskręt D, Uruska A, Zozulińska-Ziółkiewicz D. The Nondipping Blood Pattern in Type 1 Diabetes Mellitus: Pathophysiology, Complications, and Management Strategies. Endocr Pract 2025:S1530-891X(25)00062-X. [PMID: 40024374 DOI: 10.1016/j.eprac.2025.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 02/12/2025] [Accepted: 02/25/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND The nondipping blood pressure (BP) pattern, characterized by a less than 10% decline in sleep-time BP compared to awake-time values, is prevalent in individuals with type 1 diabetes mellitus (T1DM) and is associated with increased cardiovascular (CV) risk. CASE REPORT This review discusses the prevalence, pathophysiological mechanisms, complications, and management strategies of the nondipping pattern in T1DM. The nondipping pattern is linked to poor cardiac autonomic function, higher rates of albuminuria, early markers of diabetic kidney disease, and increased arterial stiffness. It is also associated with a two-fold increase in all-cause mortality. DISCUSSION Despite its clinical significance, there is no consensus on specific treatment recommendations for nondippers with T1DM. While some studies suggest that bedtime administration of antihypertensive medications, such as ACE inhibitors and angiotensin II receptor blockers, can improve the dipping pattern and reduce CV events, these findings are primarily based on studies in the general hypertensive population. Emerging evidence also indicates a potential role for vitamin D supplementation and lifestyle interventions in improving BP variability. CONCLUSION Further research is needed to develop evidence-based management strategies tailored to nondippers with T1DM, aiming to reduce CV risk and improve long-term outcomes.
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Affiliation(s)
- Michał Kulecki
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland; Doctoral School, Poznan University of Medical Sciences, Poznań, Poland.
| | - Dariusz Naskręt
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
| | - Aleksandra Uruska
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
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Siddique R, Mehmood MH, Shehzad MA. Current antioxidant medicinal regime and treatments used to alleviate oxidative stress in infertility issues. FUNDAMENTAL PRINCIPLES OF OXIDATIVE STRESS IN METABOLISM AND REPRODUCTION 2024:287-315. [DOI: 10.1016/b978-0-443-18807-7.00018-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Myke-Mbata BK, Basil B, Oloche JJ, Igbom A. Pharmacological Considerations in the Interpretation of Biochemical Results in Diabetic Patients with Cardiovascular Complications. EJIFCC 2023; 34:305-316. [PMID: 38303751 PMCID: PMC10828539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Diabetes mellitus with cardiovascular diseases is often a multi-systemic disease that requires a multi-therapeutic approach which mostly poses a challenge to laboratory result interpretation. The non-availability of information on many patients due to poor referral, documentation and record keeping has resulted in isolated interpretation of laboratory result of diabetic patients with multisystemic complications. This has led to both analytical and post-analytical errors which has a negative impact on total quality of results. Therefore, this review showed the possible therapeutic treatment of a diabetic patient with cardiovascular disease and how their pharmacological role could affect laboratory result.
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Affiliation(s)
| | - Bruno Basil
- Department of Chemical Pathology, Benue State University, Makurdi, Nigeria
| | - Jeremiah John Oloche
- Department of Pharmacology and Therapeutics, Benue State University, Makurdi, Nigeria
| | - Amarachukwu Igbom
- Department of Family Medicine, Lake District Hospital& Health Centre, Burns Lake, BC., Canada
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Macvanin MT, Gluvic Z, Bajic V, Isenovic ER. Novel insights regarding the role of noncoding RNAs in diabetes. World J Diabetes 2023; 14:958-976. [PMID: 37547582 PMCID: PMC10401459 DOI: 10.4239/wjd.v14.i7.958] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 05/01/2023] [Accepted: 05/22/2023] [Indexed: 07/12/2023] Open
Abstract
Diabetes mellitus (DM) is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. In 2021, the global prevalence of diabetes is anticipated to be 10.7% (537 million people). Noncoding RNAs (ncRNAs) appear to have an important role in the initiation and progression of DM, according to a growing body of research. The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs. miRNAs are single-stranded, short (17-25 nucleotides), ncRNAs that influence gene expression at the post-transcriptional level. Because DM has reached epidemic proportions worldwide, it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently. miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation. In this review, we address the issue of the gradually expanding global prevalence of DM by presenting a complete and up-to-date synopsis of various regulatory miRNAs involved in these disorders. We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM. We examine and synthesize recent research that used novel, high-throughput technologies to uncover ncRNAs involved in DM, necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.
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Affiliation(s)
- Mirjana T Macvanin
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Clinic for Internal Medicine, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
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Delgadillo-Centeno JS, Grover-Páez F, Hernández-González SO, Ramos-Zavala MG, Cardona-Müller D, López-Castro A, Pascoe-González S. Cinnamomum cassia on Arterial Stiffness and Endothelial Dysfunction in Type 2 Diabetes Mellitus: Outcomes of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Med Food 2023. [PMID: 37262194 DOI: 10.1089/jmf.2022.0089] [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: 06/03/2023] Open
Abstract
Cinnamomum cassia is a medicinal plant whose use has demonstrated benefits on body weight, blood pressure, glucose, and lipids. This study aimed to evaluate the effect of C. cassia on arterial stiffness and endothelial dysfunction (ED) in patients with type 2 diabetes mellitus (T2DM). A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 subjects aged 40-65 years, with a diagnosis of T2DM of one year or less since diagnosis and treated with Metformin 850 mg daily. Patients were randomly assigned to receive either C. cassia or a placebo in 1000 mg capsules, thrice a day, before each meal for 12 weeks. At baseline and after 12 weeks of intervention, brachial-ankle pulse wave velocity and Flow Mediated Dilation were measured, as well as body weight, body mass index (BMI), blood pressure (BP), fasting glucose (FG), glycated hemoglobin A1c (HbA1c), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and very low density lipoprotein cholesterol, respectively, triglycerides, creatinine, and transaminases. The Mann-Whitney U test for differences between groups and the Wilcoxon signed-rank test for intragroup differences were used, and a P ≤ .05 was considered statistically significant. After C. cassia administration, statistically significant reductions in body weight (81.4 ± 10.4 kg vs. 79.9 ± 9.0 kg, P = .037), BMI (30.6 ± 4.2 kg/m2 vs. 30.1 ± 4.2 kg/m2, P = .018), and HbA1c (53 ± 5.4 mmol/mol vs. 45 ± 2.1 mmol/mol, P = .036) were observed. No changes statistically significant on arterial stiffness, ED, FG, BP, and lipids were observed. C. cassia administration decreases body weight, BMI, and HbA1c without statistically significant changes on arterial stiffness, ED, FG, BP, and lipids. CTR Number: NCT04259606.
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Affiliation(s)
- Jesús S Delgadillo-Centeno
- Instituto de Terapéutica Experimental y Clínica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara, Jalisco, México
| | - Fernando Grover-Páez
- Instituto de Terapéutica Experimental y Clínica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara, Jalisco, México
| | - Sandra O Hernández-González
- Unidad de Investigación Biomédica 02. Instituto Mexicano del Seguro Social (IMSS), Centro Médico Nacional de Occidente, Unidad Médica de Alta Especialidad (UMAE), Hospital de Especialidades, Guadalajara, Jalisco, México
| | - María G Ramos-Zavala
- Instituto de Terapéutica Experimental y Clínica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara, Jalisco, México
| | - David Cardona-Müller
- Instituto de Terapéutica Experimental y Clínica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara, Jalisco, México
| | - Alicia López-Castro
- Unidad de Investigación Biomédica 02. Instituto Mexicano del Seguro Social (IMSS), Centro Médico Nacional de Occidente, Unidad Médica de Alta Especialidad (UMAE), Hospital de Especialidades, Guadalajara, Jalisco, México
| | - Sara Pascoe-González
- Instituto de Terapéutica Experimental y Clínica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara, Jalisco, México
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Sun J, Zhang Z, Fei Y, Gao Y, Li Z, Gao S, Wang Y, Liu J, Tu J, Wang H, Wang J, Ning X, Zhao W, Zhang W. Determinants of arterial elastic function in middle-aged and elderly people: A population-based cross-sectional study from a low-income population in China. Front Cardiovasc Med 2023; 10:1037227. [PMID: 36844726 PMCID: PMC9949891 DOI: 10.3389/fcvm.2023.1037227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/25/2023] [Indexed: 02/11/2023] Open
Abstract
Background Arterial stiffness is closely associated with the occurrence of many cardiovascular and cerebrovascular diseases. However, the risk factors and mechanisms related to arterial stiffness development have only been partially elucidated. We aimed to describe arterial elastic function and its influencing factors in middle-aged and elderly people in rural China. Methods This was a cross-sectional study conducted among residents, aged ≥45 years, of Tianjin, China, between April and July 2015. Data regarding participant demographics, medical history, lifestyle, and physical examination results were collected and assessed the association with arterial elastic function using linear regression. Results Of the 3,519 participants, 1,457 were male (41.4%). Brachial artery distensibility (BAD) decreased by 0.5%/mmHg with every 10-year increment in age. The mean BAD value was 0.864%/mmHg lower in women than in men. With each unit increase in mean arterial pressure, the BAD decreased by 0.042%/mmHg. In patients with hypertension or diabetes, the BAD decreased by 0.726 and 0.183%/mmHg, respectively, compared with those without hypertension or diabetes. For each unit increase in triglyceride (TG) level, the mean BAD increased by 0.043%/mmHg. With each increase in body mass index (BMI) category, the BAD increased by 0.113%/mmHg. Brachial artery compliance (BAC) decreased by 0.007 ml/mmHg with each 10-year increase in age, and brachial artery resistance (BAR) increased by 30.237 dyn s-1 cm-5. The mean BAC in women was 0.036 ml/mmHg lower and the mean BAR was 155.231 dyn s-1 cm-5 higher in women than in men. In individuals with hypertension, the mean BAC decreased by 0.009 ml/mmHg and the mean BAR increased by 26.169 dyn s-1 cm-5. With each increase in BMI category, the mean BAC increased by 0.005 ml/mmHg and the mean BAR decreased by 31.345 dyn s-1 cm-5. For each unit increase in TG level, the mean BAC increased by 0.001 ml/mmHg. Conclusion These findings indicate that age, sex, mean arterial pressure, BMI, diabetes, hypertension, and TG level are independently associated with the components of peripheral arterial elasticity. Understanding the factors influencing arterial stiffness is important for developing interventions to minimize arterial aging and cardiovascular and cerebrovascular diseases caused by arterial aging.
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Affiliation(s)
- Jiayi Sun
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhen Zhang
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yunhan Fei
- Department of Emergency, Tianjin Huanhu Hospital, Tianjin, China
- Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin, China
| | - Yannan Gao
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zejian Li
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Shuai Gao
- School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Yunfan Wang
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Liu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jun Tu
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
- Institute of Clinical Epidemiology and Evidence-Based Medicine, Tianjin Jizhou People’s Hospital, Tianjin, China
| | - Haiying Wang
- Department of Cardiology, Tianjin Jizhou People’s Hospital, Tianjin, China
| | - Jinghua Wang
- Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
- Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China
- Institute of Clinical Epidemiology and Evidence-Based Medicine, Tianjin Jizhou People’s Hospital, Tianjin, China
| | - Xianjia Ning
- Institute of Clinical Epidemiology and Evidence-Based Medicine, Tianjin Jizhou People’s Hospital, Tianjin, China
| | - Wenjuan Zhao
- Department of Emergency, Tianjin Huanhu Hospital, Tianjin, China
- Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin, China
| | - Wenjuan Zhang
- Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
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Chaqour B, Grant MB, Lau LF, Wang B, Urbanski MM, Melendez-Vasquez CV. Atomic Force Microscopy-Based Measurements of Retinal Microvessel Stiffness in Mice with Endothelial-Specific Deletion of CCN1. Methods Mol Biol 2023; 2582:323-334. [PMID: 36370360 DOI: 10.1007/978-1-0716-2744-0_22] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Vascular stiffness is an independent predictor of human vascular diseases and is linked to ischemia, diabetes, high blood pressure, hyperlipidemia, and/or aging. Blood vessel stiffening increases owing to changes in the microscale architecture and/or content of extracellular, cytoskeletal, and nuclear matrix proteins. These alterations, while best appreciated in large blood vessels, also gradually occur in the microvasculature and play an important role in the initiation and progression of numerous microangiopathies including diabetic retinopathy. Although macroscopic measurements of arterial stiffness by pulse wave velocity are often used for clinical diagnosis, stiffness changes of intact microvessels and their causative factors have not been characterized. Herein, we describe the use of atomic force microscopy (AFM) to determine stiffness of mouse retinal capillaries and assess its regulation by the cellular communication network (CCN) 1, a stiffness-sensitive gene-encoded matricellular protein. AFM yields reproducible measurements of retinal capillary stiffness in lightly fixed freshly isolated retinal flat mounts. AFM measurements also show significant changes in compliance properties of the retinal microvasculature of mice with endothelial-specific deletion of CCN1, indicating that CCN1 expression, or lack thereof, affects the mechanical properties of microvascular cells in vivo. Thus, AFM has the force sensitivity and the spatial resolution necessary to measure the local modulus of retinal capillaries in situ and eventually to investigate microvascular compliance heterogeneities as key components of disease pathogenesis.
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Affiliation(s)
- Brahim Chaqour
- Department of Ophthalmology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
| | - Maria B Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL, USA
| | - Lester F Lau
- Department of Biochemistry and Molecular Genetics, College of Medicine, The University of Illinois at Chicago, Chicago, IL, USA
| | - Biran Wang
- Molecular Cytology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Madern AL, Anderson NK, Colosi D, Mahdian M. The relationship between diabetes and carotid artery calcifications detected via dental cone-beam computed tomography in patients undergoing implant treatment planning. J Am Dent Assoc 2022; 153:878-883. [PMID: 35760601 DOI: 10.1016/j.adaj.2022.05.005] [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: 02/21/2022] [Revised: 05/05/2022] [Accepted: 05/17/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND The authors investigated the association between carotid artery calcifications (CACs) detected incidentally on dental cone-beam computed tomographic scans and positive diabetes status. METHODS Two patient groups were identified retrospectively from a patient database: positive for CACs based on cone-beam computed tomographic scans and positive diabetes status. In addition to demographic characteristics, data including diabetes status and presence, type, and absence of CACs were obtained. A χ2 statistical analysis was completed by means of dividing the data into sets of known CAC and known history of diabetes; significance level was P < .05. RESULTS To satisfy the a priori power analysis, records from 2010 through 2021 were used. For the positive CAC group, data were obtained from 288 patients (171 men, 117 women) and 68 patients (24%) had a positive diabetes status at the time of cone-beam computed tomography (P < .001). There were significantly more male patients (n = 47) than female patients (n = 21) with diabetes (χ2 = 9.9; P = .002). For the positive diabetes group, data were obtained from 225 patients (149 men, 76 women), and 100 patients (44%) had an identifiable CAC. There were significantly more male patients (n = 73) than female patients (n = 27) with CAC (χ2 = 21.2; P < .001). CONCLUSIONS There was a significant relationship to diabetes for patients with CACs, indicating potential undiagnosed diabetes. Male patients with diabetes are significantly more at risk of developing CACs. PRACTICAL IMPLICATIONS People with CAC may be at risk of having undiagnosed diabetes and require heightened awareness during implant treatment planning.
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Janić M, Cankar M, Šmid J, France Štiglic A, Jerin A, Šabovič M, Janež A, Lunder M. Empagliflozin-Metformin Combination Has Antioxidative and Anti-Inflammatory Properties that Correlate with Vascular Protection in Adults with Type 1 Diabetes. J Diabetes Res 2022; 2022:6796470. [PMID: 35620570 PMCID: PMC9130013 DOI: 10.1155/2022/6796470] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/10/2022] [Accepted: 04/21/2022] [Indexed: 11/24/2022] Open
Abstract
Methods 40 individuals with type 1 diabetes (average age of 44.7 ± 2.5 years) were randomized into four groups: (1) control (placebo), (2) empagliflozin 25 mg daily, (3) metformin 2000 mg daily, and (4) empagliflozin-metformin combination (25 mg and 2000 mg daily, respectively). At inclusion and after 12 weeks of treatment, the blood samples were collected, and the oxidative stress (total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, advanced oxidation protein products (AOPP), advanced glycosylation end products ((AGE) and isoprostane), and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) parameters were determined. Results The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; P < 0.01), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, P < 0.01; AGE up to 1.5-fold, P < 0.01), and decreased inflammatory parameters (up to 1.5-fold, CRP P < 0.01; IL-6 P < 0.001). Antioxidative action was associated with the improvement in arterial function (obtained in the previous study) in the empagliflozin-metformin combination group. Conclusion Empagliflozin-metformin combination has strong antioxidative and anti-inflammatory capacity, in adults with type 1 diabetes that is greater than that for the individual drugs. Its antioxidative activity at least partially explains the improvement in arterial function. Therefore, it appears that the combination provides the most powerful vascular protection.
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Affiliation(s)
- Miodrag Janić
- Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7; SI-1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
| | - Matej Cankar
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
| | - Jan Šmid
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
| | - Alenka France Štiglic
- Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Njegoševa 4, SI-1525 Ljubljana, Slovenia
| | - Aleš Jerin
- Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Njegoševa 4, SI-1525 Ljubljana, Slovenia
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia
| | - Mišo Šabovič
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
- Clinical Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška 7; SI-1000 Ljubljana, Slovenia
| | - Andrej Janež
- Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7; SI-1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
| | - Mojca Lunder
- Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7; SI-1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia
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Kulecki M, Uruska A, Naskret D, Zozulinska-Ziolkiewicz D. Arterial Stiffness and Type 1 Diabetes: The Current State of Knowledge. Curr Diabetes Rev 2022; 18:e140621194054. [PMID: 35546329 DOI: 10.2174/1573399817666210614113827] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 03/01/2021] [Accepted: 04/20/2021] [Indexed: 11/22/2022]
Abstract
The most common cause of mortality among people with type 1 diabetes is cardiovascular diseases. Arterial stiffness allows predicting cardiovascular complications, cardiovascular mortality, and all-cause mortality. There are different ways to measure arterial stiffness; the gold standard is pulse wave velocity. Arterial stiffness is increased in people with type 1 diabetes compared to healthy controls. It increases with age and duration of type 1 diabetes. Arterial stiffness among people with type 1 diabetes positively correlates with systolic blood pressure, obesity, glycated hemoglobin, waist circumference, and waist to hip ratio. It has a negative correlation with the estimated glomerular filtration rate, high-density lipoprotein, and the absence of carotid plaques. The increased arterial stiffness could result from insulin resistance, collagen increase due to inadequate enzymatic glycation, and endothelial and autonomic dysfunction. The insulin-induced decrease in arterial stiffness is impaired in type 1 diabetes. There are not enough proofs to use pharmacotherapy in the prevention of arterial stiffness, but some of the medicaments got promising results in single studies, for example, renin-angiotensin-aldosterone system inhibitors, statins, and SGLT2 inhibitors. The main strategy of prevention of arterial stiffness progression remains glycemic control and a healthy lifestyle.
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Affiliation(s)
- Michal Kulecki
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
| | - Aleksandra Uruska
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
| | - Dariusz Naskret
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznań, Poland
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Chen H, Guo Y, Cheng X. Long non-cording RNA XIST promoted cell proliferation and suppressed apoptosis by miR-423-5p/HMGA2 axis in diabetic nephropathy. Mol Cell Biochem 2021; 476:4517-4528. [PMID: 34532814 DOI: 10.1007/s11010-021-04250-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 08/20/2021] [Indexed: 12/26/2022]
Abstract
This research studied the effect of long non-coding RNA X-inactive-specific transcript (XIST) on DN. The effect of high glucose (HG) on the expression of XIST and miR-423-5p was detected by quantitative real-time PCR (qRT-PCR) in human kidney (HK) cells (human glomerular mesangial cells (HMCs) and human kidney-2 (HK-2) cells). The effect of XIST depletion and miR-423-5p inhibition or overexpression on high mobility group protein A2 (HMGA2) protein level was examined by western blot in HG-induced HK cells. The impacts of XIST depletion on viability and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assays in HG-induced HK cells. We found the expression of XIST and HMGA2 protein was significantly upregulated in DN tissues and cells. Moreover, HG treatment induced the upregulation of XIST and HMGA2 protein level in HK cells. Besides, both XIST depletion and HMGA2 depletion decreased cell proliferation but increased apoptosis in HG-treated HK cells. Furthermore, HMGA2 upregulation or miR-423-5p inhibition partly eliminated the effects of XIST depletion on cell proliferation, apoptosis of HG-treated HK cells. Interestingly, HMGA2 upregulation partly reversed miR-423-5p overexpression-mediated suppression on viability and promotion on apoptosis in HG-treated HK cells. Mechanistically, XIST sponged miR-423-5p to regulate HMGA2 expression in DN cells. Taken together, XIST depletion suppressed proliferation and promoted apoptosis via miR-423-5p/HMGA2 axis in HG-treated HK cells, which may provide a potential therapeutic target for DN.
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Affiliation(s)
- Hui Chen
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, Jiangsu, China.,Department of Endocrinology and Metabolism, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China
| | - Yuan Guo
- Clinical Laboratory Center, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China
| | - Xingbo Cheng
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, 215006, Jiangsu, China.
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Association between neutrophil–lymphocyte ratio on arterial stiffness in type-2 diabetes mellitus patients: a part of DiORS Study. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00965-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Lamacchia O, Sorrentino MR. Diabetes Mellitus, Arterial Stiffness and Cardiovascular Disease: Clinical Implications and the Influence of SGLT2i. Curr Vasc Pharmacol 2021; 19:233-240. [PMID: 32183678 DOI: 10.2174/1570161118666200317150359] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/03/2020] [Accepted: 03/04/2020] [Indexed: 12/20/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a rapidly evolving global health issue associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality. The hyperglycaemic milieu contributes to the development of CV complications via several pathological pathways, leading to increased arterial stiffness (AS), that can be considered as a predictor of CV events in patients with diabetes. The measurement of AS is increasingly used for the clinical assessment of patients. Several methodologies were used in extensive population studies to assess AS; the most commonly used is the pulse wave velocity (PWV). The cardio-ankle vascular index (CAVI) was developed to measure AS; it is not affected by blood pressure at the time of measurement and shows stable values in healthy persons for years. There are several potential pharmacological and non-pharmacological interventions aiming to reduce AS. Recent evidence from clinical trials suggests that newer antidiabetic drugs do not only exert glycaemic-lowering properties but also decrease CV risk. In this context, sodium glucose cotransporter- 2 inhibitors (SGLT2i) ( empagliflozin, canagliflozin and dapagliflozin) significantly reduced the risk of CV and all-cause mortality (only EMPA-REG OUTCOME study) and hospitalization for heart failure in patients with T2DM with established CV disease and/or with CV risk factors. Improved endothelial function and AS probably represents one of the mechanisms by which these drugs exert their beneficial effects. The present review aimed both to describe the association between AS and T2DM and to discuss the effectiveness of SGLT2i on vascular endothelial dysfunction and AS.
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Affiliation(s)
- Olga Lamacchia
- Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, via Luigi Pinto, 1, 71122 Foggia, Italy
| | - Maria Rosaria Sorrentino
- Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, via Luigi Pinto, 1, 71122 Foggia, Italy
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14
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Giordo R, Nasrallah GK, Posadino AM, Galimi F, Capobianco G, Eid AH, Pintus G. Resveratrol-Elicited PKC Inhibition Counteracts NOX-Mediated Endothelial to Mesenchymal Transition in Human Retinal Endothelial Cells Exposed to High Glucose. Antioxidants (Basel) 2021; 10:224. [PMID: 33540918 PMCID: PMC7913144 DOI: 10.3390/antiox10020224] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/23/2021] [Accepted: 01/25/2021] [Indexed: 01/09/2023] Open
Abstract
Diabetes-associated long-term hyperglycaemia leads to oxidative stress-mediated fibrosis in different tissues and organs. Endothelial-to-mesenchymal-transition (EndMT) appears to play a role in diabetes-associated fibrotic conditions. Here, we investigate whether EndMT is implicated in the diabetic retinopathy fibrotic process and evaluate the possibility that resveratrol could counteract EndMT by inhibiting high glucose (HG)-induced increases in ROS. Primary Human Retinal Endothelial Cells (HRECs) were either pre-treated for 24 h with 1 µM resveratrol or left untreated, then glucose (30 mM) was applied at 3-day intervals for 10 days. qRT-PCR and ELISA were used to detect mRNA or protein expression of endothelial markers (CD31, CDH5, vWF) or mesenchymal markers (VIM, αSMA and collagen I), respectively. Intracellular ROS levels were measured with carboxy-DCFDA, while NOX-associated ROS levels were evaluated using the NADPH-specific redox biosensor p47-roGFP. Treatment of HRECs with HG increased intracellular ROS levels and promoted phenotype shifting towards EndMT, evidenced by decreased expression of endothelial markers concomitant with increased expression of mesenchymal ones. HG-induced EndMT appears to be mediated by NADPH-associated ROS generation as pre-treatment of HRECs with resveratrol or the NADPH inhibitor, diphenyleneiodonium chloride (DPI), attenuated ROS production and EndMT transition, suggesting that the effect of resveratrol on HG-induced ROS occurs via down-regulation of NADPH oxidase. It is worth noting that resveratrol or Chelerythrine, a Protein kinase C (PKC) inhibitor, reduce ROS and EndMT in HG-exposed cells, suggesting that NADPH activation occurs via a PKC-dependent mechanism. Taken together, our results provide the basis for a resveratrol-based potential protective therapy to prevent diabetic-associated complications.
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Affiliation(s)
- Roberta Giordo
- Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates;
| | - Gheyath K. Nasrallah
- Department of Biomedical Sciences, College of Health Sciences member of QU Health, Qatar University, Doha 2713, Qatar
- Biomedical Research Center, Qatar University, Doha 2713, Qatar
| | - Anna Maria Posadino
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.M.P.); (F.G.)
| | - Francesco Galimi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.M.P.); (F.G.)
| | - Giampiero Capobianco
- Gynecologic and Obstetric Clinic, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy;
| | - Ali Hussein Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha 2713, Qatar
| | - Gianfranco Pintus
- Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.M.P.); (F.G.)
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15
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Resanović I, Zarić B, Radovanović J, Sudar-Milovanović E, Gluvić Z, Jevremović D, Isenović ER. Hyperbaric Oxygen Therapy and Vascular Complications in Diabetes Mellitus. Angiology 2020; 71:876-885. [PMID: 32638622 DOI: 10.1177/0003319720936925] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Vascular complications in patients with diabetes mellitus (DM) are common. Since impaired oxygen balance in plasma plays an important role in the pathogenesis of chronic DM-associated complications, the administration of hyperbaric oxygen therapy (HBOT) has been recommended to influence development of vascular complications. Hyperbaric oxygen therapy involves inhalation of 100% oxygen under elevated pressure from 1.6 to 2.8 absolute atmospheres in hyperbaric chambers. Hyperbaric oxygen therapy increases plasma oxygen solubility, contributing to better oxygen diffusion to distant tissues and preservation of the viability of tissues reversibly damaged by atherosclerosis-induced ischemia, along with microcirculation restoration. Hyperbaric oxygen therapy exerts antiatherogenic, antioxidant, and cardioprotective effects by altering the level and composition of plasma fatty acids and also by promoting signal transduction through membranes, which are impaired by hyperglycemia and hypoxia. In addition, HBOT affects molecules involved in the regulation of nitric oxide synthesis and in that way exerts anti-inflammatory and angiogenic effects in patients with DM. In this review, we explore the recent literature related to the effects of HBOT on DM-related vascular complications.
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Affiliation(s)
- Ivana Resanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Božidarka Zarić
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Jelena Radovanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Emina Sudar-Milovanović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran Gluvić
- Department of Endocrinology and Diabetes, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Serbia
| | - Danimir Jevremović
- Faculty of Stomatology in Pancevo, University Business Academy, Novi Sad, Serbia
| | - Esma R Isenović
- Department of Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Wang S, Zhan J, Lin X, Wang Y, Wang Y, Liu Y. CircRNA-0077930 from hyperglycaemia-stimulated vascular endothelial cell exosomes regulates senescence in vascular smooth muscle cells. Cell Biochem Funct 2020; 38:1056-1068. [PMID: 32307741 DOI: 10.1002/cbf.3543] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/22/2020] [Accepted: 03/29/2020] [Indexed: 01/14/2023]
Abstract
Vascular smooth muscle aging leads to diabetic complications such as cardiovascular and kidney diseases or diabetic foot. Therefore, understanding the mechanism of smooth muscle cell senescence in a high-glucose (HG) environment is essential. The purpose of this study was to determine whether and how circRNA from human umbilical vein endothelial cell exosomes (HUVEC-Exos) under HG conditions regulates the senescence of vascular smooth muscle cells (VSMCs). Combining circRNA array analysis and bioinformatics, we postulated that the circRNA-0077930-miR-622-Kras CeRNA network plays an important role in inducing senescence in VSMCs. CircRNA-0077930 transmitted by HG-HUVEs-Exos induced senescence of VSMCs by down-regulation of miR-622 expression and up-regulation of Kras, p21, p53 and p16 expression. Moreover, the lactate dehydrogenase (LDH) activity was significantly increased while anti-oxidative stress marker (superoxide dismutase, SOD) activity was reduced in HG-HUVEC-Exos treatment VSMCs. Finally, HG-HUVEC-Exos with depleted-circRNA-0077930 is no longer able to induce cellular senescence in VSMCs. These findings provided a new light on the effective treatment of VSMC senescence. SIGNIFICANCE OF THE STUDY: Previous studies have shown that endothelial cell senescence is closely related to smooth muscle cell aging. Here, for the first time, we proved that the HG-HUVECs derived exosomes induced the VSMCs senescence by circRNA0077930-miR622-Kras CeRNA network. The circRNA-0077930-depleted exosomes would lose the ability to promote cellular senescence of VSMCs.
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Affiliation(s)
- Sha Wang
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Junkun Zhan
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Lin
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yanjiao Wang
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yi Wang
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Youshuo Liu
- Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China
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17
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Byon CH, Kim SW. Regulatory Effects of O-GlcNAcylation in Vascular Smooth Muscle Cells on Diabetic Vasculopathy. J Lipid Atheroscler 2020; 9:243-254. [PMID: 32821734 PMCID: PMC7379086 DOI: 10.12997/jla.2020.9.2.243] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 12/20/2022] Open
Abstract
Vascular complications from uncontrolled hyperglycemia are the leading cause of death in patients with diabetes mellitus. Previous reports have shown a strong correlation between hyperglycemia and vascular calcification, which increases mortality and morbidity in individuals with diabetes. However, the precise underlying molecular mechanisms of hyperglycemia-induced vascular calcification remain largely unknown. Transdifferentiation of vascular smooth muscle cells (VSMC) into osteoblast-like cells is a known culprit underlying the development of vascular calcification in the diabetic vasculature. Pathological conditions such as high glucose levels and oxidative stress are linked to enhanced osteogenic differentiation of VSMC both in vivo and in vitro. It has been demonstrated that increased expression of runt-related transcription factor 2 (Runx2), a bone-related transcription factor, in VSMC is necessary and sufficient for the induction of VSMC calcification. Addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) moiety to the serine/threonine residues of target proteins (O-GlcNAcylation) has been observed in the arteries of diabetic patients, as well as in animal models in association with the enhanced expression of Runx2 and aggravated vascular calcification. O-GlcNAcylation is a dynamic and tightly regulated process, that is mediated by 2 enzymes, O-GlcNAc transferase and O-GlcNAcase. Glucose is metabolized into UDP-β-D-N-acetylglucosamine, an active sugar donor of O-GlcNAcylation via the hexosamine biosynthetic pathway. Overall increases in the O-GlcNAcylation of cellular proteins have been closely associated with cardiovascular complications of diabetes. In this review, the authors provide molecular insights into cardiovascular complications, including diabetic vasculopathy, that feature increased O-GlcNAcylation in people with diabetes.
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Affiliation(s)
- Chang Hyun Byon
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Soo Wan Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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18
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Sokolovska J, Stefanovics J, Gersone G, Pahirko L, Valeinis J, Kalva-Vaivode S, Rovite V, Blumfelds L, Pirags V, Tretjakovs P. Angiopoietin 2 and Neuropeptide Y are Associated with Diabetic Kidney Disease in Type 1 Diabetes Mellitus. Exp Clin Endocrinol Diabetes 2020; 128:654-662. [PMID: 31958847 DOI: 10.1055/a-1079-4711] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Serum angiopoietin 2 levels have been associated with endothelial dysfunction and diabetic kidney disease. Derangements in autonomous nervous system lead to increased production of vasoconstrictory and angiogenic mediators such as norepinephrine and neuropeptide Y and are associated with increased risk of microvascular complications. AIM To investigate associations between angiopoietin 2, neuropeptide Y and diabetic kidney disease in patients with type 1 diabetes mellitus. METHODS 289 patients with type 1 diabetes mellitus duration > 1 year were included. Patients were stratified according to presence of diabetic nephropathy (macroalbuminuria, estimated glomerular filtration rate<60 ml/min/1.73 m2 or end-stage renal disease). Angiopoietin 2 was measured by Luminex technology. Neuropeptide Y was measured by ELISA. RESULTS Patients with diabetic nephropathy had significantly increased levels of angiopoietin 2 (4020.5 (2172.4-5778.1) pg/ml vs. 2001.0 (1326.7-2862.7) pg/ml) and neuropeptide Y (18.22 (14.85-21.85) ng/ml vs. 12.91 (9.96-17.07) ng/ml). Higher levels of angiopoietin 2 and neuropeptide Y were observed also in patients with arterial hypertension. Angiopoietin 2 and neuropeptide Y correlated significantly (ρ=0.245, p<0.001). Both biomarkers were significant predictors of estimated glomerular filtration rate and diabetic nephropathy in univariate regression models. In the fully adjusted regression models and after application of a stepwise selection regression method, angiopoietin 2 demonstrated a stronger predictive power for diabetic nephropathy compared to neuropeptide Y. CONCLUSION Diabetic nephropathy is associated with increased serum concentrations of angiopoietin 2 (marker of endothelial dysfunction) and neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin 2 is a more potent predictor of diabetic nephropathy compared to neuropeptide Y.
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Affiliation(s)
| | | | - Gita Gersone
- Faculty of Medicine, Department of Human Physiology and Biochemistry, Riga Stradins University, Latvia
| | - Leonora Pahirko
- Faculty of Physics, Mathematics and Optometry, University of Latvia, Riga, Latvia
| | - Janis Valeinis
- Faculty of Physics, Mathematics and Optometry, University of Latvia, Riga, Latvia
| | | | - Vita Rovite
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Leons Blumfelds
- Faculty of Medicine, Department of Human Physiology and Biochemistry, Riga Stradins University, Latvia
| | - Valdis Pirags
- Faculty of Medicine, University of Latvia, Riga, Latvia.,Pauls Stradins Clinical University Hospital, Riga, Latvia.,Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Peteris Tretjakovs
- Faculty of Medicine, Department of Human Physiology and Biochemistry, Riga Stradins University, Latvia
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19
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Yu J, Sun H, Shang F, Wu H, Shi H, Ren L, He Y, Zhang M, Peng H. Association Between Glucose Metabolism And Vascular Aging In Chinese Adults: A Cross-Sectional Analysis In The Tianning Cohort Study. Clin Interv Aging 2019; 14:1937-1946. [PMID: 31806949 PMCID: PMC6842737 DOI: 10.2147/cia.s223690] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 10/28/2019] [Indexed: 12/31/2022] Open
Abstract
Aim Fasting glucose has been associated with vascular aging, but the association between HbA1c and vascular aging has been limitedly studied in Chinese and other ethnic populations. We aimed to examine this association in a large sample of Chinese adults. Methods In the Tianning Cohort (N=5142), fasting glucose, HbA1c, carotid-femoral pulse wave velocity (cfPWV), and pulse pressure (PP) were measured. Vascular aging was defined as having the highest quartile level of cfPWV or PP. We applied quantile regression models to examine the association between glucose metabolism and vascular aging. Results The median cfPWV was significantly increased as increasing quintiles of fasting glucose (β=0.14, P<0.001) and HbA1c (β=0.07, P=0.0056), respectively. Per 1-mmol/L increment of fasting glucose was significantly associated with a higher risk of having vascular aging defined by cfPWV (OR=1.05, P=0.022), PP (OR=1.06, P=0.048), or either (OR=1.08, P=0.002). Similarly, per 1% increment of HbA1c was significantly associated with a higher risk of having vascular aging defined by cfPWV (OR=1.06, P=0.044), PP (OR=1.10, P=0.012), or either (OR=1.12, P=0.042). Conclusion Glucose metabolism was significantly and positively associated with vascular aging in Chinese adults, but the causality is uncertain.
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Affiliation(s)
- Jia Yu
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
| | - Hongyan Sun
- Center for Disease Prevention and Control of Tianning District, Changzhou, People's Republic of China
| | - Fei Shang
- Center for Disease Prevention and Control of Tianning District, Changzhou, People's Republic of China
| | - Haishu Wu
- Center for Disease Prevention and Control of Tianning District, Changzhou, People's Republic of China
| | - Hongfei Shi
- Center for Disease Prevention and Control of Tianning District, Changzhou, People's Republic of China
| | - Liyun Ren
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
| | - Yan He
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
| | - Mingzhi Zhang
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
| | - Hao Peng
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
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Duarte SV, de Souza Rajão J, Pinho JF, Dos Santos LM, Alves-Neves CM, Magalhães GS, Ribeiro-Oliveira A, Rodrigues-Machado MDG. Changes in aortic pulse wave components, pulse pressure amplification, and hemodynamic parameters of children and adolescents with type 1 diabetes. Pediatr Diabetes 2019; 20:202-209. [PMID: 30259609 DOI: 10.1111/pedi.12782] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 09/18/2018] [Accepted: 09/19/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/OBJECTIVE Type 1 diabetes mellitus (DM1) presents important risk factors for cardiovascular events. OBJECTIVE To compare the components of the aortic pulse wave (APW) and the hemodynamic parameters among children and adolescents with DM1 and healthy individuals. METHODS This is a cross-sectional study, with 36 children and adolescents diagnosed with DM1 (11.9 ± 3.2 years) matched by sex and age with the control group (n = 36, 12.4 ± 2.9 years). The components of the APW and the hemodynamic parameters were evaluated non-invasively, using Mobil-O-Graph. RESULTS On the week of the evaluation, DM1 patients presented glycated hemoglobin (hemoglobin A1C [HbA1c]) of 9.48 ± 2.22% and fasting glycemia of 222.58 ± 93.22 mg/dL. Augmentation index (AIx@75), reflection coefficient, and augmentation pressure (AP) were significantly higher in the DM1 group (29.0 ± 9.7%, 63.0 ± 7.9, and 7.8 ± 2.7 mm Hg, respectively) compared with the control group (20.6 ± 7.9%, 53.4 ± 9.1 and 4.9 ± 2.1 mm Hg, respectively). The systolic volume (52.6 ± 11.9 and 60 ± 12.4 mL) and the cardiac output (4.3 ± 0.5 and 4.6 ± 0.5 L/min) decreased in the DM1 group in relation to the control group. The pulse pressure amplification (PPA) was significantly lower in the DM1 group (1.4 ± 0.15) compared with the control group (1.6 ± 0.17). PPA correlated negatively with total vascular resistance (TVR), AP and reflection coefficient, and positively with cardiac index in both groups. In the DMI group, the AIx@75 correlated negatively with age, height, systolic volume, and PPA, and correlated positively with the TVR and reflection coefficient. CONCLUSIONS These results confirm the presence of arterial stiffness in this population and extend the knowledge, showing, for the first time, the reduction of PPA in the DM1 group.
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Affiliation(s)
- Silvia Valadares Duarte
- Pós-Graduação Ciências Médicas, Faculdade Ciências Médicas-Minas Gerais (FCM-MG), Belo Horizonte, Brazil
| | | | - José F Pinho
- Pós-Graduação Ciências Médicas, Faculdade Ciências Médicas-Minas Gerais (FCM-MG), Belo Horizonte, Brazil
| | - Luzia M Dos Santos
- Pós-Graduação Ciências Médicas, Faculdade Ciências Médicas-Minas Gerais (FCM-MG), Belo Horizonte, Brazil
| | | | - Giselle Santos Magalhães
- Pós-Graduação Ciências Médicas, Faculdade Ciências Médicas-Minas Gerais (FCM-MG), Belo Horizonte, Brazil
| | - Antônio Ribeiro-Oliveira
- Serviço de Endocrinologia, Hospital de Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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21
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Lunder M, Janić M, Šabovič M. Prevention of Vascular Complications in Diabetes Mellitus Patients: Focus on the Arterial Wall. Curr Vasc Pharmacol 2018; 17:6-15. [DOI: 10.2174/1570161116666180206113755] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 07/16/2017] [Accepted: 11/07/2017] [Indexed: 12/14/2022]
Abstract
In Diabetes Mellitus (DM), hyperglycaemia and insulin resistance progressively lead to both
microvascular and macrovascular complications. Whereas the incidence of microvascular complications
is closely related to tight glycaemic control, this does not apply to macrovascular complications. Hyperglycaemia
influences many interweaving molecular pathways that initially lead to increased oxidative
stress, increased inflammation and endothelial dysfunction. The latter represents the initial in both types
of vascular complications; it represents the “obligatory damage” in microvascular complications development
and only “introductory damage” in macrovascular complications development. Other risk factors,
such as arterial hypertension and dyslipidaemia, also play an important role in the progression of
macrovascular complications. All these effects accumulate and lead to functional and structural arterial
wall damage. In the end, all factors combined lead to the promotion of atherosclerosis and consequently
major adverse cardiovascular events. If we accept the pivotal role of vascular wall impairment in the
pathogenesis and progression of microvascular and macrovascular complications, treatment focused
directly on the arterial wall should be one of the priorities in prevention of vascular complications in
patients with DM. In this review, an innovative approach aimed at improving arterial wall dysfunction is
described, which may show efficacy in clinical studies. In addition, the potential protective effects of
current treatment approaches targeting the arterial wall are summarised.
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Affiliation(s)
- Mojca Lunder
- Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloska cesta 7; SI-1000 Ljubljana, Slovenia
| | - Miodrag Janić
- Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloska cesta 7; SI-1000 Ljubljana, Slovenia
| | - Mišo Šabovič
- Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloska cesta 7; SI-1000 Ljubljana, Slovenia
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Henni S, Ammi M, Gourdier AS, Besnier L, Signolet I, Colas-Ribas C, Picquet J, Abraham P. Ankle brachial index is equally predictive of exercise-induced limb ischemia in diabetic and non-diabetic patients with walking limitation. J Diabetes Complications 2018; 32:702-707. [PMID: 29724591 DOI: 10.1016/j.jdiacomp.2018.03.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 02/20/2018] [Accepted: 03/25/2018] [Indexed: 01/09/2023]
Abstract
BACKGROUND In diabetic patients, arterial stiffness may impair compressibility of vessels and result in higher ankle to brachial index (ABI) than in non-diabetic subjects. METHODS We studied 1972 non-diabetic and 601 diabetic patients, with suspected peripheral artery disease, Exercise transcutaneous oxygen pressure (Ex-tcpO2), expressed in DROP index (limb tcpO2 change minus chest tcpO2 change), is insensitive to arterial stiffness and can estimate exercise-induced regional blood flow impairment (RBFI). A minimal DROP <-15 mm Hg indicates the presence of RBFI (positive test). ABI was simplified to a category variable (ABIc) by rounding ABI to the closest first decimal. RESULTS In the ABIc range 0.4 to 1.1 linear regression for mean DROP values were: y = 34 x - 53; (R2 = 0.211) and y = 33 x - 52; (R2 = 0.186) in diabetic and Non-diabetic patients, respectively. Both Db and non-D patients showed a high proportion of positive Ex-tcpO2 tests for ABIc in the normal range (ABIc: 1.0 and over) from 27.1 to up to 58%. More than half of patients with borderline ABI (ABIc = 0.9) had RBFI during exercise. it was 65.6% in diabetic and 58.5% non-diabetic patients. CONCLUSIONS Resting ABI was not a better predictor of exercise-induced RBFI in non-Db than in Diabetic patients. Our results highlights the interest of still measuring resting-ABI in diabetic patients to argue for the vascular origin of exertional limb pain, but also of performing exercise tests in patients with walking impairment.
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Affiliation(s)
- Samir Henni
- Department of Physiology and Functional Investigations, University Hospital, 49933 Angers Cedex 09, France; Mitovasc Institute, UMR INSERM 1083/CNRS 6015, University of Angers, Université Bretagne Loire, France
| | - Myriam Ammi
- Vascular and Thoracic Surgery, University Hospital, 49933 Angers Cedex 09, France
| | - Anne-Sophie Gourdier
- Department of Physiology and Functional Investigations, University Hospital, 49933 Angers Cedex 09, France
| | - Louis Besnier
- Radiology Department, University Hospital, 49933 Angers Cedex 09, France
| | - Isabelle Signolet
- Department of Physiology and Functional Investigations, University Hospital, 49933 Angers Cedex 09, France
| | - Christophe Colas-Ribas
- Department of Physiology and Functional Investigations, University Hospital, 49933 Angers Cedex 09, France
| | - Jean Picquet
- Mitovasc Institute, UMR INSERM 1083/CNRS 6015, University of Angers, Université Bretagne Loire, France; Vascular and Thoracic Surgery, University Hospital, 49933 Angers Cedex 09, France
| | - Pierre Abraham
- Department of Physiology and Functional Investigations, University Hospital, 49933 Angers Cedex 09, France; Mitovasc Institute, UMR INSERM 1083/CNRS 6015, University of Angers, Université Bretagne Loire, France.
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23
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Selvi R, Bhuvanasundar R, Angayarkanni N. Amino Acid Mixture Acts as a Potent VEGF Lowering Agent in CHO-K1 Cells Exposed to High Glucose. Arch Med Res 2017; 48:238-246. [PMID: 28923325 DOI: 10.1016/j.arcmed.2017.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 04/28/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Though the role of amino acids in Diabetes Mellitus is controversial, the beneficial effect of amino acids in Diabetes Mellitus has been reported based on its anti-glycating property and insulin potentiating effects. In the current study, we evaluated the ROS generation and VEGF expression in CHO-K1 cells induced by high glucose concentration. The effect of amino acids treatment was studied under this condition to evaluate the VEGF lowering effect. METHOD CHO-K1 cells were treated various concentration of glucose (7 mmol, 17 mmol and 27 mmol) with and without free amino acids (5 mmol) or the amino acids mixture (AAM). Intracellular reactive oxygen species (ROS) was estimated by fluorescein dye (DCFDA), nitric oxide (NO) by Griess reaction, hydrogen peroxide (H2O2) by fluorimetry using Amplex red dye, super oxide dismutase (SOD) by spectrophotometry and VEGF by immunoblotting. RESULTS High glucose condition significantly induced the expression of VEGF and this was reduced significantly by AAM treatment (p = 0.004). AAM also significantly decreased the cellular levels of ROS, NO, H2O2 as well as the SOD activity in CHO-K1 cells exposed to high glucose condition (p <0.05). CONCLUSION The present study identified AAM as a potential VEGF lowering agent that intervenes at the level of oxidative stress in high glucose conditions as evaluated in CHO-K1 cells.
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Affiliation(s)
- Radhakrishnan Selvi
- R.S.Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, Tamil Nadu, India
| | - Renganathan Bhuvanasundar
- R.S.Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, Tamil Nadu, India
| | - Narayanasamy Angayarkanni
- R.S.Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, Tamil Nadu, India.
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24
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Saha SK, Lee SB, Won J, Choi HY, Kim K, Yang GM, Dayem AA, Cho SG. Correlation between Oxidative Stress, Nutrition, and Cancer Initiation. Int J Mol Sci 2017; 18:E1544. [PMID: 28714931 PMCID: PMC5536032 DOI: 10.3390/ijms18071544] [Citation(s) in RCA: 238] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 07/12/2017] [Accepted: 07/13/2017] [Indexed: 02/07/2023] Open
Abstract
Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30-35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regulate ROS downstream mechanisms, which could have potential implications in anticancer research. Cancer initiation may be modulated by the nutrition-mediated elevation in ROS levels, which can stimulate cancer initiation by triggering DNA mutations, damage, and pro-oncogenic signaling. Therefore, in this review, we have provided an overview of the relationship between nutrition, oxidative stress, and cancer initiation, and evaluated the impact of nutrient-mediated regulation of antioxidant capability against cancer therapy.
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Affiliation(s)
- Subbroto Kumar Saha
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Soo Bin Lee
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Jihye Won
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Hye Yeon Choi
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Kyeongseok Kim
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Gwang-Mo Yang
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea.
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25
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Yi H, Peng R, Zhang LY, Sun Y, Peng HM, Liu HD, Yu LJ, Li AL, Zhang YJ, Jiang WH, Zhang Z. LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. Cell Death Dis 2017; 8:e2583. [PMID: 28151474 PMCID: PMC5386454 DOI: 10.1038/cddis.2016.451] [Citation(s) in RCA: 195] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 11/14/2016] [Accepted: 11/28/2016] [Indexed: 02/08/2023]
Abstract
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown. Our previous study has revealed that 14 lncRNAs are abnormally expressed in DN by RNA sequencing and real-time quantitative PCR (qRT-PCR) in the renal tissues of db/db DN mice. In this study, these lncRNAs were verified their expressions by qRT-PCR in mesangial cells (MCs) cultured under high- and low-glucose conditions. Twelve lncRNAs displayed the same expressional tendencies in both renal tissues and MCs. In particular, long intergenic noncoding RNA (lincRNA)-Gm4419 was the only one associating with NF-κB among these 12 lncRNAs by bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit the expressions of pro-inflammatory cytokines and renal fibrosis biomarkers, and reduce cell proliferation in MCs under high-glucose condition, whereas overexpression of Gm4419 could increase the inflammation, fibrosis and cell proliferation in MCs under low-glucose condition. Interestingly, our results showed that Gm4419 could activate the NF-κB pathway by directly interacting with p50, the subunit of NF-κB. In addition, we found that p50 could interact with NLRP3 inflammasome in MCs. In conclusion, our findings suggest lincRNA-Gm4419 may participate in the inflammation, fibrosis and proliferation in MCs under high-glucose condition through NF-κB/NLRP3 inflammasome signaling pathway, and may provide new insights into the regulation of Gm4419 during the progression of DN.
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Affiliation(s)
- Hong Yi
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Rui Peng
- Department of Bioinformatics, Chongqing Medical University, Chongqing, China
| | - Lu-Yu Zhang
- Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Yan Sun
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Hui-Min Peng
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Experimental Teaching Center, Chongqing Medical University, Chongqing, China
| | - Han-Deng Liu
- Experimental Teaching Center, Chongqing Medical University, Chongqing, China
| | - Li-Juan Yu
- Experimental Teaching Center, Chongqing Medical University, Chongqing, China
| | - Ai-Ling Li
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Ya-Juan Zhang
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Wen-Hao Jiang
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
| | - Zheng Zhang
- Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.,Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
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