Abstract 3981: MicroRNA-210 as a Novel Therapy for Treatment of Ischemic Heart Disease
Introduction: Ischemic heart disease is the leading cause of death in the United States. MicroRNAs (miRNA) are single-stranded RNA molecules of 21–23 nucleotides in length which regulate gene expression. We hypothesize miR-210, a hypoxia-induced miRNA, is a crucial regulator of angiogenesis and cell survival in response to hypoxia.
Methods: We constructed non-viral minicircle plasmid vector expressing miR-210 precursor (MC-Pre-miR-210). Adult FVB mice (n=10/group) were subject to LAD ligation followed by intramyocardial injection with
PBS as a negative control, and
minicircle carrying Fluc-GFP to monitor duration of vector expression.
Cardiac function was evaluated at weeks −1, +1, and +4 by echocardiography. For in vitro validation, we used mouse HL-1 cell line for miR-210 gain-of-function and loss-of-function study.
Results: Bioluminescence imaging indicated exogenous minicircle plasmid-mediated gene expression is stable for at least 4 weeks in the heart. Echocardiography showed significant improvement of LVEF in the MC-Pre-miR-210 (47.5%±3.0%) compared to PBS (36.1%±6.3%) at week 4. In vitro study demonstrated HL-1 transfected with miR-210 precursor can release several angiogenesis factors compared to control cells. Apoptosis assay indicate miR-210 can reduce caspase activity in HL-1 cells. Moreover, miR-210 transfected cell group showed more live cells (81.9±0.3% vs 76±0.6%; P<0.05) after hypoxia challenge.
Conclusion: miR-210 can improve angiogenesis, promote cell survive, and improve cardiac function after LAD ligation. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.