ABSTRACT
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.
ABSTRACT
The objective of the present study was to analyze the differences in the plasma microRNA (miRNA) expression profiles between patients with myocardial infarction (MI) (with or without heart failure) and individuals in a normal control group using an miRNA array. Specific miRNAs were selected to explore novel circulating markers for MI and heart failure. A total of 15 patients with heart failure and 10 patients without heart failure following acute MI (AMI) were recruited as the AMI with heart failure (AMHF) and with no heart failure (AMNHF) groups, respectively. In addition, 10 patients with an older (≥ 1 year) MI with heart failure were selected as the old MI and heart failure (OMHF) group. Finally, 10 patients with normal coronary angiograms were recruited as the control (N) group. The plasma of peripheral venous blood was collected for miRNA array detection. In the AMHF group, the expression of 17 miRNAs was upregulated and the expression of 21 miRNAs was downregulated by >1.5-fold compared with that in the AMNHF group. Compared with the N group, the expression of miRNAs in the AMNHF group was upregulated in 38 and downregulated in 48 cases by >1.5-fold. Compared with the OMHF group, 13 miRNAs were upregulated and 43 were downregulated by >1.5-fold in the AMHF group. Significant differences in the miRNA expression profiles were observed between patients with different stages of heart failure following MI and individuals in the normal control group. These differences were determined using miRNA array analysis methods based on the peripheral blood plasma. Thus, the specific miRNAs identified in this study may be novel circulating markers for MI and heart failure.