Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy
Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy
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DOI：
10.1111/j.1540-8191.2006.00296.x
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发表时间：
2006-11-01
影响因子：
1.6
通讯作者：
Woo, Y. Joseph
中科院分区：
文献类型：
--
作者：
Kolakowski, Stephen, Jr.;Berry, Mark F.;Woo, Y. Joseph
背景：心力衰竭主要由冠状动脉疾病引起，可能适用于新的血运重建疗法。这项研究评估了胎盘生长因子(PlGF)，一种强有力的血管生成剂，在缺血性心肌病大鼠模型中的作用。方法：Wistar大鼠左冠状动脉前降支高位结扎，缺血区边缘心肌直接注入PlGF(n=10)或生理盐水(n=10)。2周后，用主动脉血流探头和压力/容量电导导管评价左心室功能，组织学评价左心室几何形态，免疫荧光法评价血管生成。结果：与对照组相比，PlGF组血管生成增加(22.8+/-3.5vs.12.4+/-3.2个/高倍视野，p<；0.03)。PLGF组的室腔扩张较小(LV内径8.4±0.2比9.2±0.2 mm，p<；0.03)，交界区壁厚增加(1.85±0.1比1.38±0.2 mm，p<；0.03)。以最大左心室压(95.7±/-4比73.7+/-2毫米汞柱，p=0.001)、最大dp/dt(4206±/-362比2978+/-236毫米汞/秒，p=0.007)和射血分数(25.7+/-2比18.6+/-1%，p=0.02)来衡量，实验动物的心功能得到了改善。结论：大面积心肌梗死后心肌内注射PlGF可促进交界区血管生成，减轻不利的心室重构，保护心功能。在缺血性心力衰竭患者中，这种疗法可以作为标准血管重建术的辅助或替代方法。
Background: Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy. Methods: Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence. Results: PlGF animals had increased angiogenesis compared to controls (22.8 +/- 3.5 vs. 12.4 +/- 3.2 endothelial cells/high-powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 +/- 0.2 vs. 9.2 +/- 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 +/- 0.1 vs. 1.38 +/- 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 +/- 4 vs. 73.7 +/- 2 mmHg, p = 0.001), maximum dP/dt (4206 +/- 362 vs. 2978 +/- 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 +/- 2 vs. 18.6 +/- 1%, p = 0.02). Conclusions: Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.