Adeno-associated viral vector encoding vascular endothelial growth factor gene: Effect on cardiovascular MR perfusion and infarct resorption measurements in swine
Adeno-associated viral vector encoding vascular endothelial growth factor gene: Effect on cardiovascular MR perfusion and infarct resorption measurements in swine
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DOI：
10.1148/radiol.2432060928
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发表时间：
2007-05-01
期刊：
影响因子：
19.7
通讯作者：
Higgins, Charles B.
中科院分区：
文献类型：
--
作者：
Saeed, Maythem;Saloner, David;Higgins, Charles B.
目的：通过心血管磁共振（MR）成像评价梗死吸收和左心室（LV）功能，前瞻性地探讨心肌特异性和缺氧诱导型血管内皮生长因子（VEGF）表达基因对猪血管生成和动脉生成的影响。材料和方法：本研究符合美国国立卫生研究院指南。术后3天和8周分别对12头再灌注梗死猪进行心血管MR研究。在6头猪中，在再灌注后1小时在8个部位注射腺相关病毒（AAV）载体编码VEGF （AAV-VEGF）基因。6头猪作为对照。心血管MR测量灌注、危险面积、梗死面积和左室功能用于评估治疗。苏木精-伊红、马松三色和生物素化分离素B4染色评估区域血管密度。采用双向学生t检验来确定均值之间的显著差异。结果：AAV-VEGF对梗死后3天心血管MR灌注和梗死面积测量无影响。在8周时，治疗增加了梗死吸收、灌注和血管密度，并防止了治疗动物射血分数的恶化。与对照组（17.7% +/- 1.8至14.5% +/- 1.5,P = 0.028）相比，治疗组的增强区范围（左室表面积+/- 1.5的18.6%[平均标准误差]至9.8% +/- 1.1）显著减少。经治疗的动物的组织病理学结果显示梗死区和梗死周围区域毛细血管和动脉密度增加。与对照动物的厚壁血管相比，这些新血管活跃且薄壁。结论：AAV-VEGF可改善心血管MR测量区域心肌灌注和左室功能。(c) RSNA， 2007年。
Purpose: To prospectively determine in swine the effects of cardiac-specific and hypoxia-inducible vascular endothelial growth factor ( VEGF) expression gene on angiogenesis and arteriogenesis by using cardiovascular magnetic resonance ( MR) imaging for evaluation of infarct resorption and left ventricular ( LV) function.Materials and Methods: The investigation conformed to U. S. National Institutes of Health guidelines. Twelve pigs with reperfused infarcts were studied with cardiovascular MR 3 days and 8 weeks after surgery. In six pigs, adeno-associated viral ( AAV) vector-encoding VEGF ( AAV-VEGF) gene was injected at eight sites 1 hour after reperfusion. Six pigs served as controls. Cardiovascular MR measurements of perfusion, area at risk, infarct size, and LV function were used in evaluation of the therapy. Hematoxylin-eosin, Masson trichrome, and biotinylated isolectin B4 stains were used to assess regional vascular density. Two-way Student t test was used to determine significant differences between means.Results: AAV-VEGF had no effect on cardiovascular MR perfusion or infarct size measurements 3 days after infarction. At 8 weeks, the therapy increased infarct resorption, perfusion, and vascular density and prevented deterioration of ejection fraction in treated animals. These changes were associated with a significantly greater reduction in extent of enhanced region in treated ( 18.6% of LV surface area +/- 1.5 [ standard error of mean] to 9.8% +/- 1.1) than in control animals ( 17.7% +/- 1.8 to 14.5% +/- 1.5, P =.028). Histopathologic findings in treated animals showed increased capillary and arterial density in infarct and periinfarct regions. These new vessels were active and thin-walled compared with thick-walled vessels of control animals.Conclusion: AAV-VEGF improves cardiovascular MR measurement of regional myocardial perfusion and LV function. (c) RSNA, 2007.