西亞試劑：Combinatorial protein therapy of angiogenic and arteriogeni

Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

Huixia Lu*, Xinsheng Xu*, Mei Zhang*, Renhai Cao, Ebba Bråkenhielm, Changjiang Li*, Huili Lin*, Guihua Yao*, Huiwen Sun*, Lihang Qi*, Mengxiong Tang*, Hongyan Dai*, Yanen Zhang, Runyi Su, Yanwen Bi, Yun Zhang*,, and Yihai Cao,

*Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Public Health, Department of Cardiovascular Surgery, Qi Lu Hospital, Shandong University, Jinan 250012, Shandong Province, People's Republic of China; and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden

Communicated by Tadamitsu Kishimoto, Osaka University, Osaka, Japan, May 25, 2007 (received for review April 2, 2007)

Establishment of functional and stable collaterals in the ischemic myocardium is crucial to restoring cardiac function after myocardial infarction. Here, we show that only dual delivery of a combination of angiogenic and arteriogenic factors to the ischemic myocardium could significantly reestablish stable collateral networks and improve myocardial perfusion and function. A combination of FGF-2 with PDGF-BB, two factors primarily targeting endothelial cells and vascular smooth muscle cells, remarkably promotes myocardial collateral growth and stabilizes the newly formed collateral networks, which significantly restore myocardial perfusion and function. Using various members of the PDGF family together with FGF-2 in an angiogenesis assay, we demonstrate that PDGFR- is mainly involved in angiogenic synergism, whereas PDGFR- mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.

angiogenesis | growth factor | ischemia | myocardial infarction | neovascularization

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