Abstract
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE−/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.
Highlights
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke
Our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death
To examine whether miR26a expression was altered during endothelial apoptosis, aortic intima was harvested for real-time RT-PCR analysis (Figure 2a)
Summary
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death. Smooth muscle cell-specific overexpression of miR-145 markedly reduces atherosclerotic plaques in ApoE2/2 mice[1]. MiR-26a is a highly conserved miRNA that plays essential roles in development, cell differentiation and growth. It is frequently dysregulated in cardiovascular diseases such as cardiac hypertrophy[12,13], atrial fibrillation[14] and myocardial ischemia[15]. The present study was designed to investigate the role of miR-26a in endothelial cell apoptosis in the setting of atherosclerosis and the underlying mechanisms
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