Improvement of cardiac function in the failing rat heart after transfer of skeletal myoblasts engineered to overexpress placental growth factor.

摘要

BACKGROUND: Transplant of skeletal myoblasts is an attractive alternative to repair irreversibly damaged myocardium in ischemic heart failure. We investigated whether transplant of myoblasts overexpressing placental growth factor would stimulate angiogenesis and enhance myoblast survival in a rat heart failure model. METHODS: Three weeks after myocardial infarction, Sprague-Dawley rats in heart failure received intramyocardial injections of Ringer solution (control) or autologous myoblasts, unmodified or transfected with placental growth factor expression plasmid. Sham-operated animals served as noninfarct controls. Cardiac function was assessed by echocardiography to 86 days after engraftment. Immunocytochemistry and fluorescence imaging were used to investigate vessel formation, grafted myoblast survival, infarct wall thickness, and infarct size. Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting measured tissue messenger RNA and protein expressions. RESULTS: Left ventricular function significantly improved with time, and fractional shortening on day 86 was significantly enhanced in transfected myoblast group relative to control (P < .01) and unmodified myoblast (P < .05) groups. Vascular density (P < .01) and myoblast survival (P < .05) were enhanced in rats treated with transfected myoblasts relative to other groups (P < .05). Mean fraction of fibrotic scar tissue was decreased in unmodified and transfected myoblast groups relative to controls on day 86 (P < .05), and left ventricular wall thickness was significantly increased in transfected myoblast group relative to other groups (P < .05). CONCLUSIONS: Intramyocardial injections of autologous myoblasts overexpressing placental growth factor improved cardiac function, attenuated adverse cardiac remodeling, induced angiogenesis, and probably enhanced survival of grafted myoblasts.