Effect Of RAAV-hVEGF₁₆₅ On Rats After Acute Myocardial Infarction

Background Myocardial infarction,the leading cause of congestive heartfailure and death, presents an increase morbidity in China.Despite therecentre markable progress in medical and surgical treatment formyocardial infarction, including medical management,PTCA and CABG.However, far-ranging myocardial infarction and difuse coronary arterypathological changes usually induce severe heart failure, which is verydificult to be reversed by the treatment above.Administration of growth factors is emerging as a new therapeuticapproach for the enhancement of collateral vessel formation in theischemic heart. Recently, preliminary clinical experience with therapeuticangiogenesis suggests that this new therapeutic strategy may provideadditional blood flow to underperfused and incomplete revascularizedregions and thus be valuable in the management of these patients. Severalstudies have demonstrated that vascular endothelial growth factor (VEGF)has the potential to improve collateral development in human myocardium.Objective To determine the effects of intramyocardial injection ofrAAV-hVEGF₁₆₅ on cardiac function, ANP,ET-1,TNF-α,Angâ…¡, andexpression of Bax and Bcl-2 in a rat model of acutemyocardial infarction.Methods Eighty one male Sprague-Dawley rats weighing 260～300greceived a ligation of the left anterior decending artery to inducemyocardial infarction(MI) under intraperitoneal anaesthesia, at the sametime, 100ul rAAV-hVEGF₁₆₅ or saline was intramyocardially injected atthree seperated sites into the border zone of infarction. The models weredivided randomly into five groups: group sham operation, n=15; groupsaline, n=25; group MI, n=25; group VEGF, n=16. Echocardiograph data,Infarct size, ANP,EF-1,TNF-α,Angâ…¡,intramyocardial microvessels, VEGF expression, Bax and Bcl-2 expression in myocardium weremeasured in 4weeks after injection.Results Three rats in group sham operation, thirteen rats in group MI,fifteen rats in group saline,seven rats in group VEGF died during theexperiment. The remaining 43 rats were included in the study. Infarct sizein Group VEGF were significantly lower than those in Group MI andGroup NS (P <0.05). Echocardiograph data revealed the improvement ofejection function (EF%) in Group VEGF was greater than Group MI andGroup NS (P <0.01). Radio immunoassay indicated that ANP, ET-1,TNF-a, AngII in Group VEGF were less than Group MI and Group NS(P<0.01). Immunohistological studies showed that vessel-Counting, madeout more blood vessels in Group VEGF (P <0.01). Expression of VEGF inmyocardium in Group VEGF were higher than Group MI and Group NS(P<0.01). VEGF treatment significantly inhibited the expression of Bax,and increased expression of Bcl-2 in myocardium(P<0.01).Conclusions The current investigation shows that intramyocardialinjection of rAAV-hVEGF⁶5 is capable of significant improving of heartfunction; reducing ANP, ET-1, TNF-a, AngII, infarct size, myocyteapoptosis,and Bax expression; promoting myocardial neovascularizationand increasing Bcl-2 expression in a rat model of acute myocardialinfarction.