Sirt3 activation attenuated oxidized low-density lipoprotein-induced human umbilical vein endothelial cells’ apoptosis by sustaining autophagy

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  • This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:[10.1002/cbin.10291]

Abstract

Sirt3 is a central regulator of mitochondrial adaptation in health and disease. Our aim was to investigate the potential roles of Sirt3 in ox-LDL-treated endothelial cells. Short-term ox-LDL treatment of primary human umbilical vein endothelial cells (HUVECs) triggered autophagy, whereas long-term ox-LDL treatment resulted in apoptosis. Sirt3 expression consistently rose after short-term ox-LDL treatment and declined after long-term treatment of HUVECs. Pre-treatment with the Sirt3 activator resveratrol or Sirt3 overexpression enhanced autophagy and postponed HUVECs’ apoptosis under long-term ox-LDL treatment. In contrast, Sirt3 knockdown by siRNAs dramatically increased apoptosis of oxLDL-treated HUVECs. Resveratrol enhanced Sirt3 activity, augmenting MnSOD/SOD2 enzyme activity and expression by upregulation of FOXO3 binding and transcriptional activity at the MnSOD/SOD2 promoter. We conclude that moderate autophagy is a protective mechanism against oxidative stress over a short period. Resveratrol attenuates ox-LDL-induced endothelial cell apoptosis partially by elevating autophagy, which depends on Sirt3 participation.

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