RETRACTED: Omarigliptin Prevents TNF-α-Induced Cellular Senescence in Rat Aorta Vascular Smooth Muscle Cells (Retracted article. See vol. 35, pg. 1125, 2022)

Cellular senescence is one of the most significant factors involved in aging and age-related diseases. Senescence of vascular smooth muscle cells (VSMCs) adversely affects the function of the cardiovascular system and contributes to the development of atherosclerosis, hypertension, and other cardiovascular diseases. Glucagon-like peptide-1 (GLP-1) is an important incretin hormone involved in insulin release and vascular tone. GLP-1 is quickly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). Omarigliptin is a new DPP-4 inhibitor that has demonstrated anti-inflammatory and antioxidative stress properties. In the present study, we investigated the effects of the selective DPP-4 inhibitor omarigliptin (OMG) on VSMCs exposed to insult from tumor necrosis factor-alpha (TNF-alpha), one of the main inflammatory signaling molecules involved in cellular senescence. We found that OMG could suppress TNF-alpha-induced expression of pro-inflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6, and IL-8) and inhibit oxidative stress by reducing the production of H2O2 and protein carbonyl. OMG ameliorated the increase in senescence-associated beta-galactosidase (SA-beta-gal) and telomerase activity induced by TNF-alpha. The plasminogen activator inhibitor-1 (PAI-1)/p53/p21 pathway is a key inducer of cellular senescence. OMG ameliorated the acetylation of p53 at lysine 382 (K382) and subsequent activation of p21 via inhibition of PAI-1. Importantly, our experiments revealed that blockage of silent information-regulator 1 (SIRT1) abolished the inhibitory effects of OMG on p53 acetylation, SA-beta-gal activity, and telomerase activity in VSMCs. These results suggest that OMG may have the potential to delay or prevent the progression of age-related cardiovascular diseases by modulating the activity of SIRT1.