
circRNA HMGCS1は、miR-4521をスポンジングすることで、アルギナーゼ1の発現を上昇させ、血管内皮機能障害を悪化させる。


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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 circHMGCS1 and miR-4521 were observed in diabetes-induced vascular endothelial dysfunction. The overexpression of circHMGCS1 or silencing of miR-4521 expedited the onset of diabetes and aggravated vascular endothelial dysfunction. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging miR-4521, 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 circHMGCS1 and miR-4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and miR-4521 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.

Impact Statement Cardiovascular disease, the top cause of diabetic deaths, progresses via vascular endothelial dysfunction. This study highlights the role of circHMGCS1 and miR-4521 in diabetic vascular function and may be markers for the development of diabetic vascular endothelial dysfunction.

### Competing Interest Statement

The authors have declared no competing interest.

Circular RNA HMGCS1 sponges miR-4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction

糖尿病によって引き起こされる血管内皮機能障害を悪化させるcircrna-hmgcs1


糖尿病によって引き起こされる血管内皮機能障害を悪化させるcircRNA HMGCS1
