Chlorogenic Acid Protects Against oxLDL-Induced Oxidative Damage and Mitochondrial Dysfunction by Modulating SIRT1 in Endothelial Cells.

Abstract

Endothelial dysfunction is an important mechanism in the development of atherosclerosis and is thought to be critical for predicting cardiovascular diseases. Previous reports suggested that chlorogenic acid (CGA) is a potent antioxidant and anti-inflammatory compound. The molecular mechanisms underlying the inhibitory effects of CGA on oxLDL-induced oxidative injuries in human endothelial cells are still largely unknown. This study is aimed to test the hypothesis that CGA protects against oxLDL-facilitated oxidative stress by upregulating SIRT1 and to explore the role of AMPK/PGC-1 pathway and mitochondrial biogenesis. HUVECs were treated with oxLDL in the presence or absence of CGA pretreatment. Our data indicated that CGA pretreatment increased SIRT1 deacetylase activity levels. In addition, CGA reversed oxLDL-impaired SIRT1 and AMPK/PGC-1 activity and mitigated oxLDL-induced oxidative stress and dysfunction of mitochondrial biogenesis. However, silencing SIRT1, AMPK, and PGC-1 abated the ability of CGA to protect against oxidative stress. Results from the present study also suggested that CGA inhibits oxLDL-induced endothelial apoptosis through modulating SIRT1 and AMPK/PGC-1 function. These findings provide new insights into possible molecular mechanisms by which CGA mitigates oxLDL-induced endothelial oxidative stress and mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC-1 signaling pathway.