Collagen-binding VEGF targeting the cardiac extracellular matrix promotes recovery in porcine chronic myocardial infarction,Biomaterials Science

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Collagen-binding VEGF targeting the cardiac extracellular matrix promotes recovery in porcine chronic myocardial infarction
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-12-05 00:00:00 , DOI: 10.1039/c7bm00891k
Chunying Shi _{1,

2,

3,

4,

5} , Yannan Zhao _{6,

7,

8,

9,

10} , Yun Yang _{6,

7,

8,

9,

10} , Cheng Chen _{10,

11,

12,

13} , Xianglin Hou _{6,

7,

8,

9,

10} , Jun Shao _{10,

11,

13,

14} , Hao Yao _{10,

11,

13,

14} , Qingguo Li _{10,

11,

13,

14} , Yujun Xia _{1,

2,

3,

4,

5} , Jianwu Dai _{6,

7,

8,

9,

10}

Affiliation

An effective therapy for chronic myocardial infarction (MI) has yet to be developed. Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after MI. However, non-targeted delivery of VEGF decreases its therapeutic efficacy. In this study, for targeting the cardiac extracellular matrix, a collagen-binding domain (CBD) VEGF was used to bind specifically to the collagen-rich cardiac extracellular matrix. When intramyocardially injected into the peri-infarct region of a chronically infarcted porcine heart, CBD-VEGF attenuated the remodeling of the left ventricle with a decreased infarct size and promoted cardiomyocyte survival and angiogenesis 3 months after injection. In the 12-month trial, mature vessel networks and myocardium-like tissues were observed in the infarct region after CBD-VEGF injection. Also these beneficial effects might derive from CBD-VEGF significantly protecting cardiomyocytes from apoptosis and recruiting cardiac progenitor cells to the infarcted region. These results demonstrated that CBD-VEGF could be a promising therapeutic strategy for chronic MI.

中文翻译：

靶向心肌细胞外基质的结合胶原的VEGF促进猪慢性心肌梗死的恢复

尚未开发出有效的治疗慢性心肌梗塞（MI）的方法。心肌梗死后，血管内皮生长因子（VEGF）促进血管生成并改善心脏功能。然而，VEGF的非靶向递送降低了其治疗功效。在这项研究中，为了靶向心脏细胞外基质，使用了胶原结合结构域（CBD）VEGF与富含胶原蛋白的心脏细胞外基质特异性结合。当心肌内注射到慢性梗塞猪心脏的梗塞周围区域时，CBD-VEGF可以减少左心室的重塑，减小梗塞面积，并在注射后3个月促进心肌细胞存活和血管生成。在为期12个月的试验中，在CBD-VEGF注射后，在梗塞区域观察到了成熟的血管网络和心肌样组织。这些有益作用也可能源于CBD-VEGF，可显着保护心肌细胞免于凋亡，并将心脏祖细胞募集到梗塞区域。这些结果表明，CBD-VEGF可能是治疗慢性心肌梗死的一种有前途的治疗策略。

更新日期：2017-12-05

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