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

2007; National Academy of Sciences; Volume: 104; Issue: 29 Linguagem: Inglês

10.1073/pnas.0704966104

1091-6490

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

Fibroblast Growth Factor Research

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-α is mainly involved in angiogenic synergism, whereas PDGFR-β mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.