This Article Full Text Full Text (PDF) All Versions of this Article: 119/13/1776    most recent CIRCULATIONAHA.108.800565v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Dai, J. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Dai, J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Heart Attack Related Collections Acute myocardial infarction Related Article

(Circulation. 2009;119:1776-1784.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Collagen-Targeting Vascular Endothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction

Jing Zhang, BS^*; Liang Ding, MD^*; Yannan Zhao, BS^*; Wenjie Sun, MS; Bing Chen, PhD; Hang Lin, PhD; Xia Wang, MS; Lujie Zhang, MD; Biao Xu, MD, PhD; Jianwu Dai, PhD

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.

Correspondence to Dr Jianwu Dai, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100190, China (e-mail jwdai{at}genetics.ac.cn) or Dr Biao Xu, Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China (e-mail xubiao@medmail.com.cn).

Received June 20, 2008; accepted February 2, 2009.

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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 119: 1691-1693. [Extract] [Full Text]