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

• Published in: Molecular nutrition & food research Vol. 62; no. 11; pp. e1700928 - n/a
• Main Authors: Tsai, Kun‐Ling, Hung, Ching‐Hsia, Chan, Shih‐Hung, Hsieh, Pei‐Ling, Ou, Hsiu‐Chung, Cheng, Yung‐Hsin, Chu, Pei‐Ming
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2018
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Antioxidants; Apoptosis; Apoptosis - drug effects; Arteriosclerosis; Atherosclerosis; Biosynthesis; Cardiovascular diseases; Chlorogenic acid; Chlorogenic Acid - pharmacology; Endothelial cells; endothelial dysfunction; Heart diseases; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipoproteins, LDL - toxicity; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Molecular chains; Molecular modelling; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation - drug effects; Pretreatment; Reactive Oxygen Species - metabolism; Signal transduction; SIRT1; SIRT1 protein; Sirtuin 1 - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; AMPK; SIRT1; endothelial dysfunction; chlorogenic acid; oxidative stress
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201700928

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. Chlorogenic acid (CGA) is a potent antioxidant and anti‐inflammatory compound. This study found that CGA reduces oxLDL‐induced oxidative damage in human endothelial cells. The signaling transduction pathways of SIRT1‐mediated anti‐atherosclerotic effects involve maintaining mitochondrial biogenesis, thereby inhibiting ROS generation and oxidative stress and apoptosis.