Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia

Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia
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DOI:
10.1152/ajpheart.1998.274.3.h930
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发表时间:
1998-03-01
影响因子:
4.8
通讯作者:
Simons, M
Simons, M
中科院分区:
医学2区
文献类型:
--
作者:
Lopez, JJ;Edelman, ER;Simons, M

文献摘要

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许多肝素结合生长因子,包括碱性(bFGF)和酸性(aFGF)成纤维细胞生长因子已被证明可以促进体内血管生成。在这项研究中,我们采用缓释聚合物血管外递送系统来评估一种新型转基因aFGF在慢性心肌缺血情况下的血管生成功效。15头约克郡猪在左旋(LCX)动脉上放置Ameroid闭塞器,接受血管周围给药醋酸乙烯酯(EVAc)聚合物(10 μ g, n = 7)或单独EVAc(对照组,n = 8)的aFGF处理。7至9周后,冠状动脉造影记录ameroid诱导的冠状动脉闭塞。所有动物都进行了冠状动脉血流和整体和局部左心室功能的研究。与对照动物相比,afgf处理后ameroed受损区域的微球测定冠状动脉血流显著增加,并且这种灌注改善在心室起搏期间保持不变。离开了。心室功能研究表明,afgf治疗动物的整体和局部功能得到改善。我们的结论是,局部血管周围递送转基因aFGF可显著改善心肌血流和局部和整体左心室功能。
A number of heparin-binding growth factors, including basic (bFGF) and acidic (aFGF) fibroblast growth factors have been shown to promote angiogenesis in vivo. In this study, we employed a sustained-release polymer extravascular delivery system to evaluate the angiogenic efficacy of a novel form of genetically modified aFGF in the setting of chronic myocardial ischemia. Fifteen Yorkshire pigs subjected to Ameroid occluder placement on the left circumflex (LCX) artery were treated with perivascularly administered aFGF in ethylene vinyl acetate (EVAc) polymer (10 mu g, n = 7) or EVAc alone (controls, n = 8). Seven to nine weeks later, after coronary angiography to document Ameroid-induced coronary occlusion. all animals underwent studies of coronary flow and global and regional left ventricular function. Microsphere-determined coronary flow in the Ameroid-compromised territory was significantly increased in aFGF-treated compared with control animals, and this improvement in perfusion was maintained during ventricular pacing. Left. ventricular function studies demonstrated improved global and regional function in aFGF-treated animals. We conclude that local perivascular delivery of genetically modified aFGF results in significant improvement in myocardial flow and regional and global left ventricular function.