Scope: 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. Methods and results: 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. Conclusion: 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.
All Science Journal Classification (ASJC) codes
- Food Science