PNAS：多种生长因子参与血管调控 “生物搭桥”可治冠心病

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PNAS：多种生长因子参与血管调控 “生物搭桥”可治冠心病 促血管生长因子和促动脉生成因子联合应用，可促进心肌缺血组织血管的生成，从而改善心肌血液供应治疗冠心病。山东大学张运院士领导的心血管功能与重构研究重点实验室，与瑞典卡洛林斯卡研究院曹义海教授领导的血管再生实验室合作完成的这项研究成果，近日发表在国际权威期刊《美国科学院学报》上。这项研究得到了国家基金委海外青年学者合作研究基金和科技部“973”项目支持。据课题组成员吕慧霞介绍，缺血性心肌病（即冠心病）

  生物谷：促血管生长因子和促动脉生成因子联合应用，可促进心肌缺血组织血管的生成，从而改善心肌血液供应治疗冠心病。山东大学张运院士领导的心血管功能与重构研究重点实验室，与瑞典卡洛林斯卡研究院曹义海教授领导的血管再生实验室合作完成的这项研究成果，近日发表在国际权威期刊《美国科学院学报》上。  

  这项研究得到了国家基金委海外青年学者合作研究基金和科技部“973”项目支持。据课题组成员吕慧霞介绍，缺血性心肌病（即冠心病）主要是由于心肌的血氧供需失衡，病变的冠状动脉对心肌的灌注难以满足心肌的血氧需求而导致的。从理论上讲，最佳的治疗方法是改善冠脉的灌注。迄今为止，只有冠脉搭桥术和冠脉血管重建术等治疗方法能够做到这一点。如果能引入外源的生长因子（重组蛋白或基因），促进缺血组织血管的形成，以改善血液供应，对于缺血性心肌病来说，将是一种具有临床应用光明前景的治疗方法。这种被称为“生物搭桥”疗法的研究成为近年来医学研究的热点领域之一。但以往的研究集中于单一血管生长因子，大多只能生成结构和功能有缺陷的血管。  

  课题组研究发现，多种生长因子参与了血管生成的调控过程，促血管生长因子FGF-2在原始血管网络形成阶段起重要作用，促动脉生成因子PDGF-BB在促进血管的成熟和稳定方面起核心作用。这些因子必须在时间、空间和浓度上发挥协同作用，才能形成有功能的血管网络。动物试验结果表明，将这些生长因子制成缓释剂，包埋于梗死区周围的心肌缺血部位，缺血区心肌出现了显著增多的成熟而有功能的侧支血管网络，心肌局部血流量和收缩功能得到显著改善。（健康报）

原始出处:

Published online before print July 16, 2007, 10.1073/pnas.0704966104
PNAS | July 17, 2007 | vol. 104 | no. 29 | 12140-12145
BIOLOGICAL SCIENCES / MEDICAL SCIENCES


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 Br錵enhielm, 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