Intramyocardial injection of microRNA-210 precursor significantly improved left ventricular fractional shortening, decreased apoptosis, and increased neovascularization in a murine model of MI.
Does microRNA-210 improve cardiac function, enhance angiogenesis, and inhibit apoptosis in a murine model of myocardial infarction?
MicroRNA-210 improves angiogenesis, inhibits apoptosis, and enhances cardiac function in a murine model of myocardial infarction, suggesting potential as a novel therapy for ischemic heart disease.
BACKGROUND: MicroRNAs are involved in various critical functions, including the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart. METHODS AND RESULTS: Using microRNA microarrays, we first showed that microRNA-210 was highly expressed in live mouse HL-1 cardiomyocytes compared with apoptotic cells after 48 hours of hypoxia exposure. We confirmed by polymerase chain reaction that microRNA-210 was robustly induced in these cells. Gain-of-function and loss-of-function approaches were used to investigate microRNA-210 therapeutic potential in vitro. After transduction, microRNA-210 can upregulate several angiogenic factors, inhibit caspase activity, and prevent cell apoptosis compared with control. Afterward, adult FVB mice underwent intramyocardial injections with minicircle vector carrying microRNA-210 precursor, minicircle carrying microRNA-scramble, or sham surgery. At 8 weeks, echocardiography showed a significant improvement of left ventricular fractional shortening in the minicircle vector carrying microRNA-210 precursor group compared with the minicircle carrying microRNA-scramble control. Histological analysis confirmed decreased cellular apoptosis and increased neovascularization. Finally, 2 potential targets of microRNA-210, Efna3 and Ptp1b, involved in angiogenesis and apoptosis were confirmed through additional experimental validation. CONCLUSIONS: MicroRNA-210 can improve angiogenesis, inhibit apoptosis, and improve cardiac function in a murine model of myocardial infarction. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.
Hu et al. (2010) studied Ischemic heart disease. MicroRNA-210 precursor vs. MicroRNA-scramble or sham surgery was evaluated on Left ventricular fractional shortening, cellular apoptosis, and neovascularization. Intramyocardial injection of microRNA-210 precursor significantly improved left ventricular fractional shortening, decreased apoptosis, and increased neovascularization in a murine model of MI.