生物谷報道：來自山東大學(xué)齊魯醫(yī)院心內(nèi)科,，教育部心血管重構(gòu)和功能重點(diǎn)實(shí)驗(yàn)室（Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Public Health）,，瑞典卡羅琳學(xué)院（Karolinska Institutet）的研究人員提出angiogenic和arteriogenic因子復(fù)合蛋白治療方法能顯著提高豬心肌功能和心肌側(cè)支功能（collaterogenesis）,，為心肌缺血等心臟疾病的治療性proangiogenic/arteriogenic因子的臨床發(fā)展提供了理論性指導(dǎo)。這一研究成果公布在《美國國家科學(xué)院院刊》（PNAS）上,。
文章的通訊作者是山東大學(xué)醫(yī)學(xué)院的院長張運(yùn)院士，以及瑞典卡羅琳學(xué)院的曹一海博士（Yihai Cao，音譯）,。
心肌缺血（ischemic myocardium）是指心臟的血液灌注減少，導(dǎo)致心臟的供氧減少,，心肌能量代謝不正常，不能支持心臟正常工作的一種病理狀態(tài),。心臟的供血不是一成不變的，而是始終存在著波動,，但這種波動經(jīng)過機(jī)體自身調(diào)節(jié),，促使血液供需相對恒定,，保證心臟正常工作。如果任何一種原因引起心肌缺血,，經(jīng)機(jī)體調(diào)節(jié)不能滿足心臟工作需要,，這就構(gòu)成了真正意義上的心肌缺血。
心肌缺血治療方案主要為選擇硝酸脂類藥物（如單硝酸異山梨脂或其緩釋劑型）,，作用為擴(kuò)張心臟冠狀動脈,，增加心肌供血,；還應(yīng)該服用他汀類藥物（如阿伐他汀、辛伐他?。┮环矫娼档脱獫{中的膽固醇,，一方面穩(wěn)定動脈斑塊，防止斑塊脫落形成血栓,，造成中風(fēng)等,。
其中建立功能性和穩(wěn)定的側(cè)支循環(huán)（collaterals）是恢復(fù)缺血心肌在心肌梗塞心臟功能的關(guān)鍵點(diǎn)之一。在這篇文章中,，研究人員發(fā)現(xiàn)復(fù)合angiogenic和arteriogenic因子治療,，能高度的重建側(cè)支網(wǎng)絡(luò)，提高心肌灌注（myocardium）和功能,。
比如復(fù)合施用FGF-2 和PDGF-BB——兩種初靶定上皮細(xì)胞和脈管平滑肌細(xì)胞的因子,，就能顯著的增加心肌側(cè)支的生長，使新形成的側(cè)支網(wǎng)絡(luò)穩(wěn)定,，這對于恢復(fù)心肌灌注和心肌功能意義重大,。
利用不同的PDGF家族與FGF-2分別進(jìn)行血管新生的實(shí)驗(yàn),，研究人員進(jìn)一步發(fā)現(xiàn)PDGFR-是一種angiogenic synergism，而PDGFR-介導(dǎo)了脈管的穩(wěn)定性,。這些研究結(jié)果為心肌缺血等心臟疾病的治療性proangiogenic/arteriogenic因子的臨床發(fā)展提供了理論性的指導(dǎo),。
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
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
Fig. 1. Angiogenic synergism and vessel stability promoted by various members of the PDGF family alone or in combinations with FGF-2. Micropellets containing FGF-2 (A), PDGF-AA (B), PDGF-AB (C), PDGF-BB (D), PDGF-AA/FGF-2 (E and I), PDGF-AB/FGF-2 (F and J), or PDGF-BB/FGF-2 (G and K) together with the slow-release polymer sucrose aluminum octosulfate were implanted into the corneal micropockets of mice. Corneal neovascularization was examined on days 5 (A–H) and 70 (I–K) after growth factor implantation. The corneal neovascularization was quantitatively measured as clock hours and vessel lengths, and vascularization areas were calculated (H and L). Asterisks indicate the implanted pellets.
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