Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

• Published in: Frontiers in cell and developmental biology 2020-08, Vol.8, p.796-796
• Main Authors: Li, Chen, Tan, Ying, Wu, Jiandi, Ma, Qinghui, Bai, Shuchang, Xia, Zhangqing, Wan, Xiaoliang, Liang, Jianqiu
• Format: Article
• Language: English
• Subjects: Bnip3; Cell and Developmental Biology; mitochondria; mitophagy; oxidative stress; resveratrol
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2020.00796

Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro . Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5′ AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemia-related endothelial damage by preserving mitochondrial homeostasis.