Recombinant adenovirus encoding myocardin-related transcription factor-A prevents cardiomyocyte apoptosis induced by ischemia/reperfusion injury in rats

doi:10.3969/j.issn.2095-4344.0824

Abstract

Abstract:

BACKGROUND: Up-regulation of mRNA expression of myocardin-related transcription factor-A (MRTF-A) has been shown to be inhibit neuronal apoptosis after cerebral ischemia/reperfusion, and play a protective role in the brain. However, its effect on the apoptosis of cardiomyocytes after ischemia/reperfusion injury remains unclear.
OBJECTIVE: To investigate the effect of recombinant adenovirus encoding murine MRTF-A on the cardiomyocyte apoptosis induced by ischemia/reperfusion injury in rats.
METHODS: Sprague-Dawley rats were randomly divided into sham operation, model, blank vector and Adv-MRTF-A groups. Recombinant adenovirus encoding MRTF-A was prepared, and the models of ischemia/reperfusion injury were constructed in the rats except the sham operation group. The virus titer 1.2×1010 TU/mL of Adv-MRTF-A vector was injected into the infracted part on the left ventricular free wall in the Adv-MRTF-A group, while the rats in the blank vector group was given the injection of the same amount of blank virus. The myocardial infarct area was detected by TTC staining. The apoptosis of cardiomyocytes was detected by TUNEL method. The expression levels of MRTF-A, Bcl-2, Mcl-1 and Bax proteins in the myocardium were detected using western blot assay.
RESULTS AND CONCLUSION: The myocardial infarct area in the sham operation group was 0%. Compared with the model and blank vector groups, the myocardial infarct area in the Adv-MRTF-A group was significantly decreased (P < 0.001), the apoptotic rate of cardiomyocytes was significantly decreased (P < 0.001); the relative expression levels of MRTF-A, Bcl-2 and Mcl-1 proteins in the in the myocardium were significantly up-regulated, while the relative expression level of Bax protein was significantly down-regulated (P < 0.05). In summary, recombinant adenovirus encoding MRTF-A effectively reduces myocardial infarct ares in rats with myocardial ischemia/reperfusion injury, probably by promoting the expression levels of Bcl-2 and Mcl-1 proteins, and inhibiting the expression level of Bax protein, thereby exhibiting anti-cardiomyocyte apoptosis.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Myocardial Ischemia, Apoptosis, Tissue Engineering

CLC Number:

R318

Yang Hui1, Niu Mei-zhi1, Guo Xiao-li1, Liu Fu-lei2. Recombinant adenovirus encoding myocardin-related transcription factor-A prevents cardiomyocyte apoptosis induced by ischemia/reperfusion injury in rats[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(24): 3843-3848.

Figures/Tables 2

References

[1] 梁锐明,殷鹏,王黎君,等.中国7个城市大气PM2.5对人群心血管疾病死亡的急性效应研究[J].中华流行病学杂志,2017,38(3):283-289.

[2] Johansson S, Rosengren A, Young K, et al. Mortality and morbidity trends after the first year in survivors of acute myocardial infarction: a systematic review.BMC Cardiovasc Disord.2017;17(1):53-61.

[3] Lee MS, Dahodwala MQ.Percutaneous coronary intervention for acute myocardial infarction due to unprotected left main coronary artery occlusion: status update 2014.Catheter Cardiovasc Interv. 2015;85(3):416-420.

[4] Agrawal V,Gupta JK,Qureshi SS,et al.Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart.Indian Heart J.2016;68(6):856-861.

[5] 李文凯,尚斌,连小鹏,等.心肌缺血再灌注损伤模型大鼠经艾塞那肽预处理后心肌细胞的凋亡[J].中国组织工程研究,2015,19(17): 4288-4292.

[6] 王超,刘薇薇,黄洁,等.不同艾灸预处理时间对心肌缺血再灌注损伤大鼠心肌细胞中HIF-1α、Bcl-2及Caspase-3表达的影响[J].中医药学报,2017,45(4):70-74.

[7] 杨春,范志强,王建刚,等.七氟醚后处理减轻大鼠心肌缺血再灌注损伤及对线粒体融合蛋白2表达和PI3K-Akt通路的影响[J].中西医结合心脑血管病杂志, 2017, 15(10):1174-1177.

[8] Li Y, Xiang Y, Zhang S,et al.Intramyocardial injection of thioredoxin 2-expressing lentivirus alleviates myocardial ischemia-reperfusion injury in rats. Am J Transl Res.2017;9(10): 4428-4439.

[9] 庞英,梁明亭,马建群,等.重组人促红细胞生成素对兔心肌缺血再灌注损伤的保护作用及其机制研究[J].中华心脏与心律电子杂志, 2017,5(1):1-6.

[10] 付红光,杨现会,吕淼淼,等.乳化异氟醚后处理对大鼠心肌缺血再灌注时线粒体自噬的影响[J].中华麻醉学杂志,2017,37(5):625-628.

[11] Tan H,Chen L,Ma J.Penehyclidine hydrochloride post-conditioning reduces ischemia/reperfusion-induced cardiomyocyte apoptosis in rats.Exp Ther Med.2017;14(5): 4272-4278.

[12] Castaldi A,Chesini GP,Taylor AE,et al.Sphingosine 1-phosphate elicits RhoA-dependent proliferation and MRTF-A mediated gene induction in CPCs.Cell Signal.2016;28(8):871-879.

[13] Lamon S,Wallace MA,Russell AP.The STARS signaling pathway: a key regulator of skeletal muscle function. Pflugers Arch.2014; 466(9):1659-1671.

[14] 孙小慧,李乐.MRTF-A与心血管疾病相关性的研究进展[J].中国医药生物技术,2017,12(1):67-71.

[15] Zhong Z, Hu JQ, Wu XD, et al. Myocardin-related transcription factor-A-overexpressing bone marrow stem cells protect cardiomyocytes and alleviate cardiac damage in a rat model of acute myocardial infarction. Int J Mol Med.2015;36(3):753-759.

[16] 杜晶. MRTF-A对大鼠缺血再灌注诱导神经细胞凋亡的影响及机制研究[D].武汉科技大学,2015.

[17] Wang GF, Qi B, Tu LL, et al. Construction of adenovirus vectors encoding the lumican gene by gateway recombinant cloning technology. Int J Ophthalmol.2016;9(9):1271-1275.

[18] Medeiros VF,Azevedo ÍM,Carvalho MD,et al. The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats. Acta Cir Bras.2017;32(2):90-97.

[19] Hausenloy DJ,Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest.2013;123(1):92-100.

[20] Yang Y,Sun Y,Yi W,et al.A review of melatonin as a suitable antioxidant against myocardial ischemia-reperfusion injury and clinical heart diseases. J Pineal Res.2014;57(4):357-366.

[21] 韩江莉,何立芸,崔鸣,等.急性心肌梗死直接冠状动脉介入治疗患者微循环阻力指数检测的可行性及临床价值探讨[J].中华医学杂志, 2017, 97(29):2261-2265.

[22] 李龙,寇俊萍.动脉血栓相关治疗靶点及新药研究进展[J].中国药科大学学报,2017,48(3):251-258.

[23] 孙小慧,李乐.MRTF-A与心血管疾病相关性的研究进展[J].中国医药生物技术,2017,12(1):67-71.

[24] Lei H,Wu D,Wang JY,et al.C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res Cardiol.2015;110(4):35-41.

[25] Zhong Z,Hu JQ,Wu XD,et al.Anti-apoptotic effects of myocardin-related transcription factor-A on rat cardiomyocytes following hypoxia-induced injury. Can J Physiol Pharmacol.2016; 94(4):379-387.

[26] Lei H, Wu D, Wang JY, et al. C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res Cardiol.2015;110(4):35-42.

[27] 钟泽,胡家庆,孙勇,等. myocardin相关转录因子-A在骨髓间质干细胞治疗心肌梗死中对bcl-2基因的调控作用[J]. 中华心血管病杂志, 2015,43(6):531-536.

[28] 周勇,刘岩,杨水祥,等.腺病毒介导N-乙基顺丁烯二酰亚胺敏感因子小干扰RNA对心肌梗死大鼠心功能的影响[J].中华老年心脑血管病杂志,2014,16(9):967-970.

[29] 廖爱军,李淑晨,吴斌,等.FTY720诱导多发性骨髓瘤细胞株U266凋亡的机制研究[J].中国实验血液学杂志, 2015,23(6):1623-1627.