生物谷：促血管生長因子和促動脈生成因子聯(lián)合應(yīng)用,，可促進(jìn)心肌缺血組織血管的生成，從而改善心肌血液供應(yīng)治療冠心病,。山東大學(xué)張運(yùn)院士領(lǐng)導(dǎo)的心血管功能與重構(gòu)研究重點實驗室,，與瑞典卡洛林斯卡研究院曹義海教授領(lǐng)導(dǎo)的血管再生實驗室合作完成的這項研究成果，近日發(fā)表在國際權(quán)威期刊《美國科學(xué)院學(xué)報》上,。
這項研究得到了國家基金委海外青年學(xué)者合作研究基金和科技部“973”項目支持,。據(jù)課題組成員呂慧霞介紹，缺血性心肌?。垂谛牟,。┲饕怯捎谛募〉难豕┬枋Ш猓∽兊墓跔顒用}對心肌的灌注難以滿足心肌的血氧需求而導(dǎo)致的,。從理論上講,，最佳的治療方法是改善冠脈的灌注。迄今為止,，只有冠脈搭橋術(shù)和冠脈血管重建術(shù)等治療方法能夠做到這一點,。如果能引入外源的生長因子（重組蛋白或基因），促進(jìn)缺血組織血管的形成,，以改善血液供應(yīng),，對于缺血性心肌病來說，將是一種具有臨床應(yīng)用光明前景的治療方法,。這種被稱為“生物搭橋”療法的研究成為近年來醫(yī)學(xué)研究的熱點領(lǐng)域之一,。但以往的研究集中于單一血管生長因子，大多只能生成結(jié)構(gòu)和功能有缺陷的血管,。
課題組研究發(fā)現(xiàn),，多種生長因子參與了血管生成的調(diào)控過程，促血管生長因子FGF-2在原始血管網(wǎng)絡(luò)形成階段起重要作用,，促動脈生成因子PDGF-BB在促進(jìn)血管的成熟和穩(wěn)定方面起核心作用,。這些因子必須在時間、空間和濃度上發(fā)揮協(xié)同作用,，才能形成有功能的血管網(wǎng)絡(luò),。動物試驗結(jié)果表明，將這些生長因子制成緩釋劑,，包埋于梗死區(qū)周圍的心肌缺血部位,，缺血區(qū)心肌出現(xiàn)了顯著增多的成熟而有功能的側(cè)支血管網(wǎng)絡(luò)，心肌局部血流量和收縮功能得到顯著改善,。（健康報）
原始出處:
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 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
