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糖尿病中的内皮细胞自噬失调。

Endothelial Autophagy Dysregulation in Diabetes.

机构信息

PARCC, Inserm, Université Paris Cité, 75015 Paris, France.

出版信息

Cells. 2023 Mar 21;12(6):947. doi: 10.3390/cells12060947.

Abstract

Diabetes mellitus is a major public health issue that affected 537 million people worldwide in 2021, a number that is only expected to increase in the upcoming decade. Diabetes is a systemic metabolic disease with devastating macro- and microvascular complications. Endothelial dysfunction is a key determinant in the pathogenesis of diabetes. Dysfunctional endothelium leads to vasoconstriction by decreased nitric oxide bioavailability and increased expression of vasoconstrictor factors, vascular inflammation through the production of pro-inflammatory cytokines, a loss of microvascular density leading to low organ perfusion, procoagulopathy, and/or arterial stiffening. Autophagy, a lysosomal recycling process, appears to play an important role in endothelial cells, ensuring endothelial homeostasis and functions. Previous reports have provided evidence of autophagic flux impairment in patients with type I or type II diabetes. In this review, we report evidence of endothelial autophagy dysfunction during diabetes. We discuss the mechanisms driving endothelial autophagic flux impairment and summarize therapeutic strategies targeting autophagy in diabetes.

摘要

糖尿病是一个重大的公共卫生问题,2021 年全球有 5.37 亿人受到影响,预计在未来十年这个数字还将继续增加。糖尿病是一种全身性代谢疾病,会导致严重的大血管和微血管并发症。内皮功能障碍是糖尿病发病机制中的一个关键决定因素。功能失调的内皮细胞通过减少一氧化氮的生物利用度和增加血管收缩因子的表达导致血管收缩,通过产生促炎细胞因子导致血管炎症,导致微血管密度降低,从而导致器官灌注不足、促凝状态和/或动脉僵硬。自噬是一种溶酶体回收过程,似乎在内皮细胞中发挥着重要作用,确保内皮细胞的稳态和功能。先前的报告已经提供了证据,证明 I 型或 II 型糖尿病患者存在自噬通量受损。在这篇综述中,我们报告了糖尿病期间内皮细胞自噬功能障碍的证据。我们讨论了驱动内皮细胞自噬通量受损的机制,并总结了针对糖尿病的自噬治疗策略。

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