Angiogenic growth factors and/or cellular therapy for myocardial regeneration: A comparative study
Angiogenic growth factors and/or cellular therapy for myocardial regeneration: A comparative study
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DOI：
10.1016/j.jtcvs.2004.04.007
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发表时间：
2004-08-01
影响因子：
6
通讯作者：
Carpentier, AF
中科院分区：
文献类型：
--
作者：
Chachques, JC;Duarte, F;Carpentier, AF
背景：局部输送血管生成生长因子和细胞植入已被提议用于心肌梗死患者，而不可能经皮或手术重建术。本研究的目的是比较这些技术在心肌梗死实验模型中的效果。方法：采用结扎2根冠状动脉的方法，造左室心肌梗死27只。梗死形成后3周，随机分为4组。1组，向梗死区注射培养基（对照组）；2组行自体成肌细胞植入；3组给予血管内皮生长因子治疗；第4组同时注射血管内皮生长因子和成肌细胞。评估包括血清肌钙蛋白IC水平，超声心动图（二维和彩色运动），以及用于定量分析毛细血管的免疫组织学研究（术后3个月）。结果：4只动物在心肌梗死期间死于难治性心室颤动；2例死于中风，2例死于感染。梗死后第2天血清肌钙蛋白升高至45.6 +/- 4.7 ng/mL。3个月时超声心动图显示细胞组（57 +/- 11.1 mL）和细胞+血管内皮生长因子组（58.6 +/- 6.6 mL：对照组，74.4 +/- 11.2 mL；血管内皮生长因子组，68.1 +/- 3.4 mL）左室扩张明显受限。彩色超声显示细胞组（从13.6% +/- 0.8%到21.1% +/- 1.5%）和细胞+血管内皮生长因子组（从12.8% +/- 0.9%到18.7% +/- 2.3%）的局部分数面积变化有重要改善。血管内皮生长因子组梗死周围毛细血管数量增加（1036 +/- 75支：对照组785 31支；细胞组830 75支；细胞加血管内皮生长因子组831 83支）。结论：与血管内皮生长因子组和对照组相比，细胞治疗组局部心室收缩性改善，心脏扩张受限；因此，缺血后重构减少。血管内皮生长因子组出现血管新生，但心室功能和重构未见改善。为了改善细胞存活的局部条件，需要进一步研究血管生成治疗心肌疤痕的预血管化。
Background: Locally delivered angiogenic growth factors and cell implantation have been proposed for patients with myocardial infarcts without a possibility of percutaneous or surgical revascularization. The goal of this study was to compare the effects of these techniques in an experimental model of myocardial infarct.Methods: Left ventricular myocardial infarction was created in 27 sheep by ligation of 2 coronary arteries. Three weeks after creation of the infarct, animals were randomized into 4 groups. In group 1, sheep received a culture medium injection to the infarct area (control group); group 2 underwent autologous myoblast implantation; group 3 received vascular endothelial growth factor; and group 4 received injection of both vascular endothelial growth factor and myoblasts. Evaluation included serum troponin IC levels, echocardiography (2-dimensional and color kinesis), and immunohistologic studies for quantitative analysis of capillaries (3 months after surgery).Results: Four animals died of refractory ventricular fibrillation during myocardial infarction; 2 died after surgery because of stroke and 2 because of infections. Serum troponin increased to 45.6 +/- 4.7 ng/mL at postinfarction day 2. Echocardiography at 3 months showed a significant limitation of left ventricular dilation in the cell group (57 +/- 11.1 mL) and in the cell plus vascular endothelial growth factor group (58.6 +/- 6.6 mL: control group, 74.4 +/- 11.2 mL; vascular endothelial growth factor group, 68.1 +/- 3.4 mL). Color kinesis echography showed important improvements of regional fractional area change in the cell group (from 13.6% +/- 0.8% to 21.1% +/- 1.5%) and in the cell plus vascular endothelial growth factor group (from 12.8% +/- 0.9% to 18.7% +/- 2.3%). The number of capillaries increased in the peri-infarct region of the vascular endothelial growth factor group (1036 +/- 75: control group, 785 3 1; cell group, 830 75; cell plus vascular endothelial growth factor group, 831 83).Conclusions: In the cell therapy groups, regional ventricular contractility improved and heart dilatation was limited compared with either vascular endothelial growth factor or control; thus, postischemic remodeling was reduced. Angiogenesis was demonstrated in the vascular endothelial growth factor group, without improvement of ventricular function and remodeling. To improve local conditions for cell survival, further studies are warranted on prevascularization of myocardial scars with angiogenic therapy.