SIRT2 is down-regulated in myocardial infarction mice and regulates reparative angiogenesis via targeting AKT signaling pathway

Myocardial infarction (MI) remains one of the most deadly diseases worldwide with elusive mechanisms and limited treatment measures. Recent evidences showed that several histone deacetylase (HDAC) family proteins were involved in the pathogenesis of MI, especially in the process of reparative angiogenesis. Here, we first explored the expression level of SIRT2, an Nicotinamide Adenine Dinucleotide-Dependent deacetylase, in a mouse MI model. Then we further studied the function of SIRT2 on angiogenesis using human umbilical vein endothelial cells (HUVECs). As the result, we observed that the expression level of SIRT2 was down-regulated in endothelial cells isolated from ischemic but not remote myocardium early after MI. Knockdown of SIRT2 attenuated the angiogenesis ability of HUVECs, while overexpression of SIRT2 increased the angiogenesis ability. In addition, knockdown of SIRT2 decreased the level of phosphorylated AKT, which was a well-known modulator of reparative angiogenesis after MI in published literatures. Furthermore, the down-regulation of SIRT2 increased the acetylation level of AKT and beta-catenin, suggesting the potential activity change in the both proteins. In conclusion, our results revealed that SIRT2 promoted reparative angiogenesis of HUVECs via targeting AKT signaling pathway. Reparative angiogenesis based on SIRT2 might provide theoretical basis for targeted therapy of MI patients.