Dapagliflozin suppresses vascular smooth muscle cell senescence by promoting autophagy

Background Vascular aging is a key pathogenesis of cardiovascular diseases. Dapagliflozin (Dapa) could significantly improve cardiovascular outcomes, but its effect on vascular aging remains elusive. Objectives Present study explored the effect of Dapa on vascular aging. Methods Vascular smooth cells (VSMCs) aging was induced by angiotensin II (AngII) in mice and H202 in human VSMCs. Senescence-associated β-galactosidase and senescence markers (including p21 and p53) were evaluated in the presence and absence of Dapa. Associated pathways were explored by RNA-Seqs and gene ontology (GO) analysis. Results Dapa significantly reduced vascular aging in vivo as expressed by reduced pulse wave velocity. Dapa significantly reduced the expression of senescence-associated β-galactosidase, senescence markers (p53, p21) and age-related inflammatory cytokines (TGF-β/IL-6) in vascular tissue from AngII treated mice, and in human VSMCs treated by H202, and enhanced cell migration and proliferation in human VSMCs treated by H202. GO enrichment analysis indicated that Dapa attenuated VSMCs aging by modulating autophagy pathway. Mechanistically, p62 knockdown reversed the beneficial effects of Dapa, indicating that Dapa could attenuate vascular aging process through activating autophagy in the in vivo and in vitro aging models. Conclusions This study reveals that Dapa could suppresses vascular aging via promoting autophagy.