LAUSR

ABSTRACT SIRT6, with both deacetylase and ADP‐ribosyltransferase activities, is predominantly expressed in the nucleus. It has been revealed that SIRT6 regulates various biological functions including metabolism, aging and stress resistance. This study aims to investigate the role of SIRT6 in vascular inflammation and it molecular mechanism. We found that tumor necrosis factor‐&agr; (TNF‐&agr;) did not alter the localization of SIRT6 in vascular adventitial fibroblasts (VAFs), vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The expression of SIRT1, SIRT6 was decreased in TNF‐&agr;‐treated VAFs. In contrast, TNF‐&agr; significantly increased the expression of monocyte chemotactic protein 1 (MCP‐1) and interleukin (IL) −6. Knockdown of SIRT1 and SIRT6 by siRNA significantly enhanced TNF‐&agr;‐induced expression of MCP‐1 and IL‐6, respectively. Overexpression of SIRT1 and SIRT6 inhibited TNF‐&agr;‐induced expression of MCP‐1 and IL‐6 in VAFs. Moreover, we also found SIRT1 positively regulated the expression of SIRT6 in VAFs. In addition, knockdown of SIRT1 and SIRT6 respectively augmented TNF‐&agr;‐induced generation of reactive oxygen species (ROS) and phosphorylation of protein kinase B (Akt). ROS scavenger N‐acetyl‐l‐cysteine (NAC) and Akt inhibitor MK2206 reduced TNF‐&agr;‐induced mRNA expression of MCP‐1 and IL‐6 in VAFs. In vivo studies indicated that the expression of SIRT1, SIRT6 was decreased and the expression of MCP‐1, IL‐6 and IL‐1&bgr; was increased in carotid collar‐induced vascular inflammation. Taken together, these findings indicate that SIRT1 and SIRT6 inhibit TNF‐&agr;‐induced inflammation in VAFs by ROS and Akt pathway. Graphical abstract Figure. No caption available. HighlightsTNF‐&agr; did not alter the localization of SIRT6 in VECs, VSMCs and VAFs.SIRT1 positively regulates expression of SIRT6 in VAFs.SIRT1 and SIRT6 inhibited TNF‐&agr;‐induced MCP‐1 and IL‐6 expression in VAFs through ROS and Akt pathway.