Effects of Exogenous Nerve Growth Factor on Late Reperfusion after Myocardial Infarction_Journal of Biomedical Engineering

Authors：

刘洋 , 张绍敏 , 孙春丽 ,  吴锦晖 , LIUYang , ZHANGShaomin , SUNChunli ,  WUJinhui

四川大学华西医院老年医学中心/老年病科, 成都 610041;
Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

吴锦晖, Email: wujinhui@scu.edu.cn; WUJinhui, Email: wujinhui@scu.edu.cn

Keywords：

nerve growth factor; myocardial infarction; late reperfusion; ventricular remodeling

DOI：

10.7507/1001-5515.20150230

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This study demonstrates that nerve growth factor (NGF) plays a protective role in myocardial infarction and early reperfusion by reducing the myocardial cell apoptosis and by improving ventricular remodeling and seeks to assess the effects and mechanisms of NGF on late reperfusion after myocardial infarction. The models of late reperfusion were established by ligating the left main coronary artery and then cutting the suture 2 hours after coronary artery ligation. The rats in NGF treatment group were injected 10μL Ad-NGF (by constructing the adenovirus vector Ad-NGF containing NGF gene) at four locations around infarction. The rats in adenoviral vector (Adv) group were injected 10μL adenoviral cector as the NGF group. The late reperfusion group and the sham group were given normal saline as above, and the sham group underwent thracotomy without coronary ligation. On the 3rd, 7th, 14th and 28th day after operation, we investigated the role of NGF on late reperfusion by recording cardiac structure and function with echocardiography, by examining the expression of NGF andⅧfactor with immunohistochemical method, and by evaluating the myocardial cell apoptosis with terminal dUTP nick end-labeling method (TUNEL). We found that the NGF group had higher expression of NGF protein (P < 0.01) and lower apoptosis index (AI) (P < 0.01 or P < 0.05) compared to the late reperfusion group and Adv group on all time points. The NGF group had remarkably higher level of neovascularization compared to the late reperfusion group on the 14th day (P < 0.01) and the 28th day (P < 0.05). The NGF group also had higher LVEF and FS levels compared to the late reperfusion group on the 14th day (P=0.006, P=0.006) and on the 28th day (P=0.000, P=0.000). Whereas the NGF group had lower LVEDD, LVESD (P=0.038, P=0.000) and lower LVEDV, LVESV (P=0.001, P=0.000) on the 28th day compared to late reperfusion group. In this experiment, the NGF gene carried by adenovirus vector had been trans-fected and obviously increased the expression of NGF protein in NGF group. NGF may help postpone the myocardial remodeling and improve the heart function by promoting the myocardial neovascularization and inhibiting myocardial apoptosis.

Citation： 刘洋, 张绍敏, 孙春丽, 吴锦晖, LIUYang, ZHANGShaomin, SUNChunli, WUJinhui. Effects of Exogenous Nerve Growth Factor on Late Reperfusion after Myocardial Infarction. Journal of Biomedical Engineering, 2015, 32(6): 1294-1301. doi: 10.7507/1001-5515.20150230 Copy

1.	CAPORALI A, SALA-NEWBY G B, MELONI M, et al. Identification of the prosurvival activity of nerve growth factor on cardiac myocytes[J]. Cell Death Differ, 2008, 15(2):299-311.
2.	于小华, 张新刚, 王时俊, 等.神经生长因子在小鼠病毒性心肌炎心肌中表达的意义[J].临床儿科杂志, 2006, 24(5):402-405.
3.	黄志军, 袁洪, 曾钧发, 等.重组腺相关病毒载体介导人血管内皮生长因子165基因对缺血心肌血管新生的影响[J].中国动脉硬化杂志, 2004, 12(6):627-631.
4.	王云, 冯震博, 陈罡, 等.改进的TUNEL技术在检测急性心肌梗死大鼠心肌细胞凋亡中的应用[J].广西医科大学学报, 2009, 26(5):684-686.
5.	李东野, 闫艳, 朱红, 等.HIF-1α基因对心肌梗死后心肌细胞凋亡和心功能影响的实验研究[J].中国病理生理杂志, 2008, 24(2):275-278.
6.	MELONI M, CAPORALI A, GRAIANI G, et al. Nerve growth factor promotes cardiac repair following myocardial infarction[J]. Circ Res, 2010, 106(7):1275-1284.
7.	任福强, 石应康, 郭应强, 等.大鼠急性心肌梗死模型建立方法的改进[J].生物医学工程学杂志, 2009, 26(6):1291-1294.
8.	GOVONI S, PASCALE A, AMADIO M, et al. NGF and heart:Is there a role in heart disease?[J]. Pharmacol Res, 2011, 63(4):266-277.
9.	KRYZHNOVSKIǏ S A, VITITNOVA M B. Cardiovascular effects of nerve growth factor analytical review. Part 2[J]. Fiziol Cheloveka, 2011, 37(3):109-128.
10.	RAHBEK U L, DISSING S, THOMASSEN C, et al. Nerve growth factor activates aorta endothelial cells causing PI3K/Akt-and ERK-dependent migration[J]. Pflugers Arch, 2005, 450(5):355-361.
11.	EMANUELI C, SALIS M B, PINNA A, et al. Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs[J]. Circulation, 2002, 106(17):2257-2262.
12.	PARK M J, KWAK H J, LEE H C, et al. Nerve growth factor induces endothelial cell invasion and cord formation by promoting matrix metalloproteinase-2 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway and AP-2 transcription factor[J]. J Biol Chem, 2007, 282(42):30485-30496.
13.	HASSANKHANI A, STEINHELPER M E, SOONPAA M H, et al. Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells[J]. Dev Biol, 1995, 169(1):309-321.
14.	KAYE D M, VADDADI G, GRUSKIN S L, et al. Reduced myocardial nerve growth factor expression in human and experimental heart failure[J]. Circ Res, 2000, 86(7):E80-E84.

1. CAPORALI A, SALA-NEWBY G B, MELONI M, et al. Identification of the prosurvival activity of nerve growth factor on cardiac myocytes[J]. Cell Death Differ, 2008, 15(2):299-311.
2. 于小华, 张新刚, 王时俊, 等.神经生长因子在小鼠病毒性心肌炎心肌中表达的意义[J].临床儿科杂志, 2006, 24(5):402-405.
3. 黄志军, 袁洪, 曾钧发, 等.重组腺相关病毒载体介导人血管内皮生长因子165基因对缺血心肌血管新生的影响[J].中国动脉硬化杂志, 2004, 12(6):627-631.
4. 王云, 冯震博, 陈罡, 等.改进的TUNEL技术在检测急性心肌梗死大鼠心肌细胞凋亡中的应用[J].广西医科大学学报, 2009, 26(5):684-686.
5. 李东野, 闫艳, 朱红, 等.HIF-1α基因对心肌梗死后心肌细胞凋亡和心功能影响的实验研究[J].中国病理生理杂志, 2008, 24(2):275-278.
6. MELONI M, CAPORALI A, GRAIANI G, et al. Nerve growth factor promotes cardiac repair following myocardial infarction[J]. Circ Res, 2010, 106(7):1275-1284.
7. 任福强, 石应康, 郭应强, 等.大鼠急性心肌梗死模型建立方法的改进[J].生物医学工程学杂志, 2009, 26(6):1291-1294.
8. GOVONI S, PASCALE A, AMADIO M, et al. NGF and heart:Is there a role in heart disease?[J]. Pharmacol Res, 2011, 63(4):266-277.
9. KRYZHNOVSKIǏ S A, VITITNOVA M B. Cardiovascular effects of nerve growth factor analytical review. Part 2[J]. Fiziol Cheloveka, 2011, 37(3):109-128.
10. RAHBEK U L, DISSING S, THOMASSEN C, et al. Nerve growth factor activates aorta endothelial cells causing PI3K/Akt-and ERK-dependent migration[J]. Pflugers Arch, 2005, 450(5):355-361.
11. EMANUELI C, SALIS M B, PINNA A, et al. Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs[J]. Circulation, 2002, 106(17):2257-2262.
12. PARK M J, KWAK H J, LEE H C, et al. Nerve growth factor induces endothelial cell invasion and cord formation by promoting matrix metalloproteinase-2 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway and AP-2 transcription factor[J]. J Biol Chem, 2007, 282(42):30485-30496.
13. HASSANKHANI A, STEINHELPER M E, SOONPAA M H, et al. Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells[J]. Dev Biol, 1995, 169(1):309-321.
14. KAYE D M, VADDADI G, GRUSKIN S L, et al. Reduced myocardial nerve growth factor expression in human and experimental heart failure[J]. Circ Res, 2000, 86(7):E80-E84.

Journal of Biomedical Engineering

Effects of Exogenous Nerve Growth Factor on Late Reperfusion after Myocardial Infarction

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