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. Conclusion-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. (Circulation. 2010;122[suppl 1]:S124 -S131.)Key Words: gene therapy Ⅲ ischemic heart disease Ⅲ microRNA Ⅲ minicircle vector I schemic heart disease is the number 1 cause of morbidity and mortality in the United States owing to aging, obesity, diabetes, and other comorbid diseases. One potent therapeutic approach for ischemic heart disease is to reduce oxygen consumption, inhibit cardiomyocyte apoptosis, increase coronary flow, and induce revascularization. MicroRNAs (miRNAs), representing approximately 1% of the eukaryotic transcriptome, is an evolutionarily conserved family of noncoding RNAs of 20 to 22 nucleotides that negatively regulate the expression of protein-coding genes through translational inhibition and RNA decay. miRNAs are involved in diverse biological progresses, including cellular differentiation, proliferation, angiogenesis, and apoptosis. 1 To date, 721 miRNAs have been discovered in human and 597 miRNAs in the mouse according to the miRBase Sequence Database Release 14 (www.mirbase.org/). miRNAs can regulate approximately 30% human protein-coding genes. 2 Importantly, the successful suppression of murine liver cancer by systemic delivery of miR-26a suggests the potential of using miRNAs as a novel therapeutic tool. 3 In th...

The extent of the arterial injury is associated with different patterns of perfusion restoration. The double coagulation mouse model is, in our hands, the best model for studying new therapeutic approaches as it offers a therapeutic window in which improvements can be monitored efficiently.

Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen–dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy.