on March 23, 2009
Published online before print March 23, 2009, doi: 10.1161/CIRCULATIONAHA.108.800565
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Submitted on June 20, 2008
From Key Laboratory of Molecular Developmental Biology (J.Z., Y.Z., W.S., B.C., H.L., X.W., J.D.), Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China; Graduate School, Chinese Academy of Sciences (J.Z., Y.Z.), Beijing, China; and Department of Cardiology (L.D., L.Z., B.X.), Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. * To whom correspondence should be addressed. E-mail: xubiao{at}medmail.com.cn
or jwdai{at}genetics.ac.cn.
Background—Vascular endothelial growth factor (VEGF) is an important active protein for the induction of angiogenesis and improvement in cardiac function after myocardial ischemia; however, the lack of a delivery system targeted to the injured myocardium reduces the local therapeutic efficacy of VEGF and increases its possible adverse effects. Methods and Results—We produced a fusion protein (CBD-VEGF) consisting of VEGF and a collagen-binding domain (CBD). The fusion protein specifically bound to type I collagen in vitro. In addition, CBD-VEGF promoted human umbilical vein endothelial cell proliferation after binding to collagen, which indicates that it retained both growth factor activity and collagen-binding ability. When implanted subcutaneously in rats, collagen membranes loaded with CBD-VEGF were significantly vascularized. After it was injected into rats with acute myocardial infarction, CBD-VEGF was largely retained in the cardiac extracellular matrix, in which collagen I was rich. Four weeks after VEGF or CBD-VEGF was injected into the infarct border zone, cardiac function detected by echocardiography and hemodynamics was preserved in the CBD-VEGF group. Administration of CBD-VEGF also induced reduction of scar size, whereas native VEGF did not have these effects. In addition, a significant increase in the number of capillary vessels in infarcted hearts was found in the CBD-VEGF group. Conclusions—The injection of CBD-VEGF improved cardiac function in rats with induced acute myocardial infarction. This could potentially provide a new treatment option for myocardial infarction.
Accepted on February 2, 2009
Collagen-Targeting Vascular Endothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction
Jing Zhang BS,
Key words: vascular endothelial growth factors • collagen • angiogenesis • myocardial infarction
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