Sirtuin 6 attenuates angiotensin II-induced vascular adventitial aging in rat aortae by suppressing the NF-κB pathway

Abstract

Adventitia-induced vascular remodeling plays an important role in vascular aging. However, the mechanism remains unclear. In this study, we found that sirtuin 6 (SIRT6) expression was downregulated in the aortae of aged rats compared with those of young rats. Adventitial fibroblasts (AFs) were isolated and cultured from rat aortae to clarify the relationship between SIRT6 expression and vascular aging. Lentivirus-mediated SIRT6 knockdown promoted the aging phenotype in AFs, affecting proliferation, collagen secretion, migration, and α-smooth muscle actin expression. Moreover, angiotensin II (Ang II) decreased SIRT6 expression, activated the NF-κB pathway, and led to vascular aging. The NF-κB pathway inhibitor BAY 11-7082 reduced Ang II-induced nuclear translocation of the NF-κB p65 subunit and other effects of Ang II, such as AF proliferation, collagen secretion, and migration. Mechanistically, SIRT6 suppression increased acetyl-NF-κB p65 (Lys310) expression and NF-κB transcriptional activity in SIRT6-knockdown AFs. SIRT6 could directly bind to the p65 subunit and attenuate Ang II-induced NF-κB activation and vascular aging. In summary, this study was the first to correlate SIRT6 expression and adventitia-induced vascular senescence. SIRT6 maybe a biomarker of vascular aging, and activating SIRT6 maybe a therapeutic strategy for delaying vascular aging.