Sirt1/Drp1通路通过抑制线粒体过度分裂减少糖尿病患者心脏微血管内皮细胞损伤

IF 2.8 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Shimeng Huang, Yuanbo Gao, Ying Wang, Siyu Zhao, Bing Lu, Aibin Tao
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引用次数: 0

摘要

背景:糖尿病患者心脏微血管明显减少,同时伴有糖尿病心脏并发症发生率的显著增加和死亡率的增加。本研究旨在探讨sirtuin 1 (Sirt1)在糖尿病心脏微血管内皮细胞损伤中的作用及其可能机制。方法:建立2型糖尿病小鼠模型和心脏微血管内皮细胞(CMEC)模型。采用血小板内皮细胞粘附分子1 (CD31)免疫组化检测心脏微血管密度(MVD)。用MitoSOX检测线粒体活性氧(ROS),并用线粒体染色观察线粒体形态。通过划痕和血管生成试验评估cmec的血管生成。我们用细胞计数试剂盒(CCK)-8测定细胞活力,用乳酸脱氢酶(LDH)释放法测定细胞损伤。我们使用TUNEL染色、Caspase-3活性和Western blot来评估细胞凋亡。结果:Sirt1蛋白表达的降低伴随着2型糖尿病小鼠心脏微血管密度的降低。在高糖和棕榈酸处理cmes 48 h后,我们发现Sirt1和动力蛋白相关蛋白1 (Drp1) Ser637磷酸化蛋白的表达降低,而Cleaved Caspase-3蛋白的表达升高。内皮细胞血管生成能力下降,线粒体ROS和线粒体分裂增加,内皮细胞损伤加重,内皮细胞凋亡增加。在基因和药物水平上Sirt1蛋白表达和功能的增加,通过增加Drp1 Ser637的磷酸化,减轻了线粒体过度分裂,减少了细胞凋亡,改善了CMECs的功能。结论:在糖尿病条件下,Sirt1/Drp1通路通过抑制线粒体过度分裂来减轻对cmec的损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sirt1/Drp1 Pathway Reduces Microvascular Endothelial Cell Injury in Diabetic Pateints' Hearts by Inhibiting Excessive Mitochondrial Division.

Background: Cardiac microvessels are significantly reduced in diabetic patients, which is accompanied by a significant increase in the incidence of diabetic cardiac complications and increased mortality. This study aimed to investigate the role and possible mechanism of sirtuin 1 (Sirt1) in microvascular endothelial cell injury in diabetic hearts.

Methods: Type 2 diabetes mouse models and cardiac microvascular endothelial cell (CMEC) cell models were established. Cardiac microvessel density (MVD) was detected using Platelet- Endothelial Cell Adhesion Molecule 1 (CD31) immunohistochemistry. Mitochondrial reactive oxygen species (ROS) was detected with MitoSOX and morphology was observed with mitochondrial staining. CMECs angiogenesis was evaluated via scratch and angiogenesis assays. We measured cell viability with a Cell Counting Kit (CCK)-8 assay and cell injury with lactate dehydrogenase (LDH) release assay. We assessed apoptosis using TUNEL staining, Caspase-3 activity, and Western blot.

Results: The decrease in Sirt1 protein expression was accompanied by a decrease in cardiac microvessel density in type 2 diabetic mice. After 48 h of treating the CMECs with high-glucose and palmitic acid, it was discovered that the expression of Sirt1 and dynamin-related protein 1 (Drp1) Ser637 phosphorylated protein decreased, while the expression of Cleaved Caspase-3 protein increased. Also, the angiogenesis ability of endothelial cells was decreased, while mitochondrial ROS and mitochondrial division were increased, which culminated in aggravated endothelial cell injury and increased endothelial cell apoptosis. Increased Sirt1 protein expression and function at the gene and drug levels alleviated excessive mitochondrial division, reduced apoptosis, and improved the function of CMECs by increasing the phosphorylation of Drp1 Ser637.

Conclusion: Under diabetic conditions, the Sirt1/Drp1 pathway reduces injury to CMECs by inhibiting excessive mitochondrial division.

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来源期刊
Current vascular pharmacology
Current vascular pharmacology 医学-外周血管病
CiteScore
9.20
自引率
4.40%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Current Vascular Pharmacology publishes clinical and research-based reviews/mini-reviews, original research articles, letters, debates, drug clinical trial studies and guest edited issues to update all those concerned with the treatment of vascular disease, bridging the gap between clinical practice and ongoing research. Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials. Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units).
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