المؤلفون: Zhiliang Zhang, Yesheng Ling, Zhuoshan Huang, Junlin Zhong, Qian Chen, Jinlai Liu, Xixiang Tang, Long Peng

الوصف: Purpose: Mitophagy reduces mitochondrial dysfunction and accumulation of reactive oxygen species (ROS) to prevent myocardial injury in diabetic cardiomyopathy (DCM). Accumulated studies have confirmed that metformin enhances autophagy to maintain mitochondrial homeostasis and scavenge ROS. However, whether and how metformin regulates mitophagy in cardiomyocytes remain unclear. Methods: Diabetic cardiomyopathy was modeled in H9c2 Cardiomyocytes treated with high glucose (30 mM) . Then high Glucose-stimulated H9C2 cells were exposed to metformin, AMPKα inhibitor and Sirt1 inhibitor for 24 h. Mitochondrial dysfunction and mitophagy were detected by fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), mitochondrial membrane potential(MMP), flow cytometry and western blot. Resluts: We found that the protein expression of Parkin, ROS level, and mitochondrial membrane potential showed dynamic changes in H9C2 cells under the stimulation of high glucose. Importantly, metformin enhanced mitophagy, scavenged ROS, improved mitochondrial function and inhibited apoptosis in H9C2 cells treated with high glucose. Mechanistically, metformin increased the protein expression of p-AMPKα, Sirt1, Parkin, and LC3-II in H9C2 cells after a high glucose challenge. Depletion of AMPKα and Sirt1 abolished the increase of protein levels of Parkin and LC3-II and mitophagy levels induced by metformin. Conclusion: Our data indicated that metformin improves mitochondrial dysfunction of H9C2 cells under hyperglycemia by activating AMPKα/Sirt1/Parkin-mediated mitophagy, which provides novel evidence for the treatment of DCM.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::e7d47a8ef19600395ac6179b74ab6910
https://doi.org/10.21203/rs.3.rs-2281485/v1

المؤلفون: Xujing Xie, Yanting Luo, Long Peng, Zexiong Li, Jinlai Liu, Xiaosi Yuan, Jieming Zhu, Zhuoshan Huang

مصطلحات موضوعية: medicine.medical_specialty, business.industry, Internal medicine, Propensity score matching, medicine, Case-control study, Cardiology, Type 2 Diabetes Mellitus, In patient, Atrial fibrillation, medicine.disease, business

الوصف: Background Compared to people without diabetes, people with type 2 diabetes mellitus (T2DM) have an increased risk of developing atrial fibrillation (AF). Possible predictors of AF have not been adequately investigated in T2DM. We aimed to identify the factors associated with AF in such patients. Methods A total of 2,682 patients with T2DM, who was admitted to Department of Cardiovascular Medicine, the Third Affiliated Hospital, Sun Yat-sen University between 1 June, 2015 to 1 Nov, 2019, were enrolled in the study. 641 patients were excluded. There were 122 patients with AF and 1,919 patients without AF. 1:1 propensity scores match was performed according to age and gender. Patients were divided into the two groups: with AF (122patients) and without AF (122patients). Clinical, demographic, echocardiographic, laboratorial data and medicine were compared between the groups. Results There was significant statistical difference in neutrophil, monocyte, creatinine, total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B100 (ApoB100), monocyte to high-density lipoprotein ratio (MHR), fasting glucose (FG), left atrial diameter (LAD), ejection fraction(EF), antiplatelet therapy and the prevalence of heart failure between the two groups. On multivariate logistic regression analysis, the increase of MHR, FG and LAD, as well as the decrease of TC and antiplatelet therapy were independent predictors of AF. On receiver operating characteristic (ROC) curve analysis, using a cut-off level of 0.568, MHR predicted AF with a sensitivity of 65.6%, a specificity of 76.2%, and an AUC of 0.736(95% CI 0.673-0.800). Using a cut-off level of 0.507, the combination of TC, MHR, FG, LAD and antiplatele therapy predicted AF with a sensitivity of 73.0%, a specificity of 84.4%, and an AUC of 0.862(95% CI 0.816-0.907). Conclusions The increase of MHR, FG and LAD, as well as the decrease of TC and antiplatelet therapy were independent predictors of AF. MHR only, as well as the combination of TC, MHR, FG, LAD and antiplatelet therapy can better predict the risk of AF in patients with T2DM.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::16549b7580836f2a4d70ad51c78a50f6
https://doi.org/10.21203/rs.2.24738/v1