Vascular endothelial growth factor gene transfer improves host endothelialization of xenogeneic biologic heart valve in vivo.
OBJECTIVE
To investigate the feasibility of endothelialization of bioprosthesis by transfer of vascular endothelial growth factor (VEGF) gene.


METHODS
Bovine pericardium treated with glutaraldehyde and L-glutamic acid was positioned into the pig right atrium. pcD(2)/hVEGF(121) gene (1 mg) was transferred into the right ventricular myocardium using surgical sutures Reverse transcri ption polymerase chain reaction (RT PCR) was employed to evaluate the expression of myocardial VEGF mRNA. The determination of concentrations of VEGF protein in blood from both the right atrium and peripheral vein, and histological and ultrastructural analysis of implanted bovine pericardium were completed simultaneously.


RESULTS
The concentration of VEGF derived from the right atrium in pcD(2)/hVEGF(121) group was significantly higher than that in the pcD(2) group 10 days after VEGF gene transfer (P < 0.01). The expression of myocardial VEGF mRNA in pcD(2)/hVEGF(121) group was much higher in comparison with that in the pcD(2) group. The morphological analysis demonstrated that the coverage rate of host endothelium in the pcD(2)/hVEGF(121) group was 2.6 times as fast as that in the pcD(2) group at 16 days after VEGF(121) gene transfer (P < 0.01). Entire endothelialization occurred at 30 days after VEGF gene transfer. In addition, higher expression of myocardial VEGF mRNA was still available.


CONCLUSIONS
VEGF gene transfer by surgical suture can remarkably accelerate endothelialization of bioprosthesis, which may provide a new approach for inhibiting biological valve calcification and improve biocompatibility and long-term durability of the bioprosthesis.
Zhang
Zhongming
Z
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, China.
Dong
Hongyan
H
Liu
Jindong
J
Wang
Wei
W
Hu
Bo
B
D000818:Animals; D001705:Bioprosthesis; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D018014:Gene Transfer Techniques; D006350:Heart Valve Prosthesis; D006801:Humans; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors