Lu Huixia, Xu Xinsheng, Zhang Mei, Cao Renhai, Bråkenhielm Ebba, Li Changjiang, Lin Huili, Yao Guihua, Sun Huiwen, Qi Lihang, Tang Mengxiong, Dai Hongyan, Zhang Yanen, Su Runyi, Bi Yanwen, Zhang Yun, Cao Yihai
Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Public Health, Qi Lu Hospital, Shandong University, Jinan 250012, Shandong Province, People's Republic of China.
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12140-5. doi: 10.1073/pnas.0704966104. Epub 2007 Jul 16.
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-alpha is mainly involved in angiogenic synergism, whereas PDGFR-beta mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.
在缺血心肌中建立功能性和稳定的侧支循环对于心肌梗死后恢复心脏功能至关重要。在此，我们表明，仅向缺血心肌双重递送血管生成因子和动脉生成因子的组合，可显著重建稳定的侧支循环网络，并改善心肌灌注和功能。FGF-2与PDGF-BB（两种主要靶向内皮细胞和血管平滑肌细胞的因子）的组合，可显著促进心肌侧支生长并稳定新形成的侧支循环网络，从而显著恢复心肌灌注和功能。在血管生成试验中，将PDGF家族的各种成员与FGF-2一起使用，我们证明PDGFR-α主要参与血管生成协同作用，而PDGFR-β介导血管稳定性信号。我们的研究结果为用于治疗缺血性心脏病的促血管生成/动脉生成因子的临床开发提供了概念性指导方针。
