ABSTRACT
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 ß-cells induced ß-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+ T cells. These actions help stifle the creation of unstable plaque characterized by thinner fibrous caps, larger necrotic cores, heightened inflammation, and more extensive vascular calcification-features seen in advanced atherosclerotic lesion development. Additionally, serum SELENOS could function as a potential biomarker, and SELENOS single nucleotide polymorphisms (SNPs) rs4965814, rs28628459, and rs9806366, might be effective gene markers for atherosclerosis-related diseases in diabetes. This review accentuates the pathophysiological processes of atherosclerosis in diabetes and amasses current evidence on SELENOS's potential therapeutic benefits or as predictive biomarkers in the various stages of diabetes-induced atherosclerosis.
ABSTRACT
Therapy with mesenchymal stem cells (MSCs) is considered an attractive strategy for the repair or regeneration of damaged tissues. However, low survival of MSCs limits their applications clinically. Oxidized low-density lipoprotein (ox-LDL) is significantly increased in patients with hyperlipidemia and decreases the survival of MSCs. Bcl-2 is critically involved in important cell functions, including cell membrane integrity and cell survival. The present study was designed to test the hypothesis that ox-LDL attenuates the survival of MSCs through suppression of Bcl-2 expression. Bone marrow MSCs from C57BL/6 mice were cultured with ox-LDL at different concentrations (0-140 µg/mL) for 24 h with native LDL as control. Ox-LDL treatment substantially decreased the survival of MSCs dose-dependently and enhanced the release of intracellular lactate dehydrogenase (LDH) in association with a significant decrease in Bcl-2 protein level without change in BAX protein expression in MSCs. Bcl-2 overexpression effectively protected MSCs against ox-LDL-induced damages with preserved cell numbers without significant increase in LDH release. Treatment with N-acetylcysteine (NAC) (1 mM) effectively preserved Bcl-2 protein expression in MSCs and significantly attenuated ox-LDL-induced decrease of cell number and increase in the release of intracellular LDH. These data indicated that ox-LDL treatment resulted in a significant damage of cell membrane and dramatically decreased the survival of MSCs dose-dependently through inhibition of Bcl-2 expression. NAC treatment significantly protected MSCs against the damage of cell membrane by ox-LDL and promoted the survival of MSCs in association with preserved Bcl-2 expression.