Aerobic Exercise Modulates Sirt1 to Alleviate Diabetic Arterial Remodeling

Abstract

Metabolic reprogramming is a pivotal driver of diabetic vascular remodeling by inducing the phenotypic transition of vascular smooth muscle cells (VSMCs). This study demonstrated that in the aortas of diabetic mice, the medial layer was significantly thickened, with disordered arrangement of collagen and elastic fibers, downregulated expression of the contractile marker α-smooth muscle actin (α-SMA), and upregulated expression of the synthetic marker osteopontin (OPN). These pathological changes were accompanied by suppressed Sirtuin 1 (Sirt1) expression and increased glycolytic enzyme activity. Our results further demonstrated that an 8-week treadmill exercise intervention effectively restored aortic Sirt1 levels in diabetic mice, ameliorated mitochondrial damage, normalized elevated glycolysis in VSMCs, and attenuated their transition to a synthetic phenotype. Collectively, these findings demonstrate that aerobic exercise-induced improvements in diabetic vascular remodeling are accompanied by alterations in Sirt1 expression, glucose metabolism, mitochondrial morphology, and the VSMC phenotype.