Effects of Adenovirus-mediated VEGF165 Gene Therapy on Myocardial Infarction.

AIM: To evaluate the role of adenovirus-mediated transduction human VEGF isoform 165 via direct myocardial injection in rats with an occluded circumflex coronary artery, and the possible underlying mechanism.

METHODS: Sprague-Dawley rats were induced myocardial infarction (MI) with ligation of the left coronary artery. Rats were randomly divided into 4 groups: 1) the sham group; 2) the MI group; 3) the NS (normal saline) group and 4) the VEGF group. Direct myocardial injection of 0.1 ml rAAV-hVEGF165 (virus titer, 2×1010 v.p./ml) was performed in the border zone of myocardial infarction in the VEGF group at 3 different sites, whereas 0.1 ml of normal saline was injected in the NS group. 4 weeks after treatment, the serum levels of atrial natriuretic peptide (ANP), angiotensin-II (Ang II), tumor necrosis factor-α (TNF-α), and endothelin-1 (ET-1) were detected by competitive radioimmunoassay. The level of VEGF, Bax, and Bcl-2 was assessed by IHC.

RESULTS: The whole heart weight, left heart weight, heart mass index and left heart mass index in the VEGF group were higher than those in the MI and NS group. VEGF treatment could also significantly increase cardiac function, and increase microvessel density in the infarcted area. Moreover, VEGF treatment could decrease the serum neurohumoral factors (ANP, Ag II, and TE-1), and inhibit myocardial apoptosis via TNF-α, Bax, and Bcl-2.

CONCLUSION: Adenovirus-mediated VEGF165 gene therapy could significantly improve cardiac function possibly by inducing myocardial collateral vessel development, inhibiting the apoptosis of myocardial cells, and inhibiting ventricular remodeling.