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.
A high sensitive sandwich-type electrochemical biosensor utilizing capture probe (CP), target probe (TP), and signal probe (SP) was first developed for specific detection of microRNA-26a (miR-26a), a biomarker with diagnostic significance for atherosclerosis. In general, gold nanoparticles (Au NPs) were electrodeposited on to a glassy carbon electrode to enhance conductivity, followed by immobilization of 5 ′- thiolated CP through a gold-sulfur bond. Subsequently, the modified electrode was hybridized with the mixture of miR-26a and 3′-biotin-tagged SP in sequence. Furthermore, horseradish peroxidase-streptavidin (HRP) with potent reducing capability was finally grafted on the SP via the strong affinity between biotin and streptavidin. Additionally, the fabrication process of the miR-26a biosensor was thoroughly investigated. Based on the dual amplification mechanism facilitated by Au NPs and HRP-catalytic activity, the proposed biosensor demonstrated outstanding electrochemical properties, including good reproducibility and stability, as well as high sensitivity for miR-26a detection down to 0.88 fM with a linear range from 1 fM to 1 nM. The biosensor also displayed exact specificity, which could discriminate miR-26a from a range of base mismatched microRNAs. Moreover, it was successfully applied to the determination of miR-26a in serum samples. In conclusion, given the excellent analytical performance, this biosensor shows promise for potential use in clinical diagnostics for atherosclerosis.
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