Current views on selenoprotein S in the pathophysiological processes of diabetes-induced atherosclerosis: potential therapeutics and underlying biomarkers.

Atherosclerotic cardiovascular disease (ASCVD) consistently ranks as the primary mortality factor among diabetic people. A thorough comprehension of the pathophysiological routes and processes activated by atherosclerosis (AS) caused by diabetes mellitus (DM), together with the recognition of new contributing factors, could lead to the discovery of crucial biomarkers and the development of innovative drugs against atherosclerosis. Selenoprotein S (SELENOS) has been implicated in the pathology and progression of numerous conditions, including diabetes, dyslipidemia, obesity, and insulin resistance (IR)-all recognized contributors to endothelial dysfunction (ED), a precursor event to diabetes-induced AS. Hepatic-specific deletion of SELENOS accelerated the onset and progression of obesity, impaired glucose tolerance and insulin sensitivity, and increased hepatic triglycerides (TG) and diacylglycerol (DAG) accumulation; SELENOS expression in subcutaneous and omental adipose tissue was elevated in obese human subjects, and act as a positive regulator for adipogenesis in 3T3-L1 preadipocytes; knockdown of SELENOS in Min6 β-cells induced β-cell apoptosis and reduced cell proliferation. SELENOS also participates in the early stages of AS, notably by enhancing endothelial function, curbing the expression of adhesion molecules, and lessening leukocyte recruitment-actions that collectively reduce the formation of foam cells. Furthermore, SELENOS forestalls the apoptosis of vascular smooth muscle cells (VSMCs) and macrophages, mitigates vascular calcification, and alleviates inflammation in macrophages and CD4