Treating Synergistically Myocardial Infarction Of Rats With VEGF₁₆₅ And Angiopoietin-1

Purpose This study was designed to evaluate the effects of VEGF165 and angiopoietins-l(Angl) on arteriogenesis angiogenesis in the rat ischemic myocardium and on cell mobilizing and therapy of the infarct rats. Methods Replication-deficient adenovirus encoding for human VEGF165 or angiopoietin-1 were amplified. Myocardial ischemia was induced in male rats by ligation of the left anterior descending(LAD) coronary artery.Ad5-VEGF165or Ad5-Angl or Ad5-GFP at 10 PFU was injected into the ischemic myocardium immediately following LAD ligation.Brdu(50mg/kg) was administered 1 week after ligation.At the second and fourth week,the hearts were harvested and sectioned for immunohistochemistry examination. Capilliary density and collateral vessel formation were counted at four different fields on each slide. Anti-factor VIII ,anti-actin and anti-myosin heavy chain(MHC) were employed to stain endothelial cells(ECs),smooth muscle cells(SMCs) and cardiac myocytes(CMS).Number of Brdu(+) cells were counted at four different fields on each slide.M-mode echocardiography wasused to evaluated the cardiac function at the first and fourth week. Result Both VEGF165 and Angl significanly increased capillary density compared to ligation control.Angl significantly increased collateral vessel formation. VEGF/Angl significantly increased the number of arteriocapillaries.VEGF165 and Angl significanly increased number of Brdu(+) endothelial cells(ECs) and cardiac myocytes(CMS) compared to control. VEGF and Angl also significantly improve the cardiac function. . Conclusion The results suggest that the combination of VEGF and Angl gene therapy can increase both angiogenesis and arteriogenesis The results also suggest that the combination of VEGF and Angl gene therapy can mobilize stem cell to area of myocardial ischemia and improve the cardiac function of infarct rats.so they have important prospect and value of clinical application.