Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.
Ningbo Innovation Center, Zhejiang University, Ningbo, China.
Elife. 2024 Sep 5;13:RP97267. doi: 10.7554/eLife.97267.
Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of and were observed in diabetes-induced human umbilical vein endothelial cell dysfunction. Persistent inhibition of accelerated development and exacerbated vascular endothelial dysfunction in diabetic mice. Mechanistically, upregulated arginase 1 by sponging , leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of and in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of and could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.
非编码 RNA 作为内皮细胞功能的新型调节因子发挥着关键作用。2 型糖尿病被认为是心血管疾病的主要诱因，由于糖脂代谢和氧化应激诱导的异常，它在血管内皮细胞功能障碍中起着至关重要的作用。在这项研究中，观察到糖尿病诱导的人脐静脉内皮细胞功能障碍中 和 的异常表达水平。持续抑制 加速了糖尿病小鼠的发展，并加剧了血管内皮功能障碍。在机制上， 通过海绵吸附 而上调精氨酸酶 1，导致血管一氧化氮分泌减少和内皮型一氧化氮合酶活性抑制，以及粘附分子表达增加和细胞活性氧产生增加，血管舒张减少，加速血管内皮功能障碍。总之，这些发现阐明了 和 在糖尿病引起的心血管疾病中的生理作用和相互作用机制，表明调节 和 的表达可能是预防与糖尿病相关的心血管疾病的一种潜在策略。此外，我们的发现为揭示 ncRNAs 在糖尿病及其相关并发症中的 ncRNAs 调节作用提供了一条新的技术途径。
