切换至 "中华医学电子期刊资源库"

中华临床医师杂志(电子版) ›› 2018, Vol. 12 ›› Issue (02) : 103 -106. doi: 10.3877/cma.j.issn.1674-0785.2018.02.009

所属专题: 文献

综述

心肌梗死后心肌纤维化的研究进展
姚德山1, 张振刚1, 龚开政1,()   
  1. 1. 225001 扬州大学附属医院心血管内科
  • 收稿日期:2017-08-26 出版日期:2018-01-15
  • 通信作者: 龚开政
  • 基金资助:
    国家自然科学基金(81270197,81470381,81770262); 江苏省重点研发计划社会发展项目资助(BE2015663)

Progress in research of myocardial fibrosis after myocardial infarction

Deshan Yao1, Zhengang Zhang1, Kaizheng Gong1,()   

  1. 1. Department of Cardiology, the Affiliated Hospital of Yangzhou University, Yangzhou 225001, China
  • Received:2017-08-26 Published:2018-01-15
  • Corresponding author: Kaizheng Gong
  • About author:
    Corresponding author: Gong Kaizheng, Email:
引用本文:

姚德山, 张振刚, 龚开政. 心肌梗死后心肌纤维化的研究进展[J]. 中华临床医师杂志(电子版), 2018, 12(02): 103-106.

Deshan Yao, Zhengang Zhang, Kaizheng Gong. Progress in research of myocardial fibrosis after myocardial infarction[J]. Chinese Journal of Clinicians(Electronic Edition), 2018, 12(02): 103-106.

心肌纤维化是心肌梗死后主要的病理过程,特征是细胞外基质合成和降解失衡,而成纤维细胞和肌纤维母细胞在此过程中起重要作用。心肌梗死后,梗死区域替代性纤维化可以减少梗死区域进一步的扩张,维持心室结构完整性,防止心室壁破裂;而非梗死区域的反应性纤维化,则会改变心室顺应性,增加心室壁的硬度,影响心脏的收缩和舒张功能。因此,心肌梗死后理想的治疗是抑制非梗死区域反应性纤维化、诱导梗死区域心肌再生,从而改善心功能。

Myocardial fibrosis is the main pathological process during the post-myocardial infarction phase (post-MI), which is characterized by the imbalance between extracellular matrix (ECM) synthesis and degradation, in which fibroblasts and myofibroblasts play an important role. Replacement fibrosis can reduce the further expansion of the infarction area, maintain ventricular integrity, and prevent ventricular wall rupture after MI. However, reactive fibrosis in the infarct border zone and in the remote uninjured myocardium leads to altered chamber compliance and increased ventricular stiffness, thereby compromising cardiac output. Therefore, an ideal therapy for MI-induced cardiac injury would combine the inhibition of reactive fibrosis (and other remodeling processes) in non-infarct areas with the induction of the regeneration of the infarcted myocardium to improve heart function.

1
Laflamme MA, Murry CE. Regenerating the Heart [J]. Nat Biotechnol, 2005, 23(23): 845-856.
2
Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodelling [J]. Nat Rev Cardiol, 2014, 11(5): 255-265.
3
Francis Stuart SD, De Jesus NM, Lindsey ML, et al. The crossroads of inflammation, fibrosis, and arrhythmia followingmyocardial infarction [J]. J Mol Cell Cardiol, 2015, 91: 114-122.
4
李龙, 杨水祥. 心衰与心律失常的关联和发展 [J]. 中国心血管病研究, 2016, 14(2): 105-108.
5
Ripplinger CM, Lou Q, Li W, et al. Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: Implications for low-voltage cardioversion [J]. Heart Rhythm, 2009, 6(1): 87-97.
6
Kohl P, Gourdie RG. Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue? [J]. J Mol Cell Cardiol, 2014, 70(100): 37-46.
7
Istrătoaie O, Pirici I, Ofiţeru AM, et al. Evaluation of cardiac microvasculature in patients with diffuse myocardial fibrosis [J]. Rom J Morphol Embryol, 2016, 57(4): 1351-1356.
8
Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis [J]. Cell Mol Life Sci, 2014, 71(4): 549-574.
9
Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-β signaling in cardiac remodeling [J]. J Mol Cell Cardiol, 2011, 51(4): 600-606.
10
Desmoulière A, Geinoz A, Gabbiani F, et al. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts [J]. J Cell Biol, 1993, 122(1): 103-111.
11
Lighthouse JK, Small EM. Transcriptional control of cardiac fibroblast plasticity [J]. J Mol Cell Cardiol, 2015, 91: 52-60.
12
Bujak M, Ren G, Kweon HJ, et al. Essential Role of Smad3 in Infarct Healing and in the Pathogenesis of Cardiac Remodeling [J].Circulation, 2007, 116 (19): 2127-2138.
13
Weber KT, Sun Y, Bhattacharya SK, et al. Myofibroblast-mediated mechanisms of pathological remodelling of the heart [J]. Nat Rev Cardiol, 2013, 10(1): 15-26.
14
Rodríguez-Pascual F, Busnadiego O, González-Santamaría J. The profibrotic role of endothelin-1: Is the door still open for the treatment of fibrotic diseases? [J]. Life Sci, 2014, 118(2): 156-164.
15
Leask A. Getting to the heart of the matter: new insights into cardiac fibrosis [J]. Cir Res, 2015, 116(7): 1269-1276.
16
Mueller EE, Momen A, Massé S, et al. Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy [J]. Cardiovasc Res, 2011, 89(3): 623-633.
17
Kohan DE, Cleland JG, Rubin LJ, et al. Clinical trials with endothelin receptor antagonists: what went wrong and where can we improve? [J]. Life Sci, 2012, 91(13-14): 528-539.
18
Muraoka N, Ieda M. Direct reprogramming of fibroblasts into myocytes to reverse fibrosis [J]. Annu Rev Physiol, 2014, 76(76): 21-37.
19
Fu JD, Srivastava D. Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine [J]. Circ J, 2015, 79(2): 245-254.
20
Srivastava D, Yu P. Recent advances in direct cardiac reprogramming [J]. Curr Opin Genet Dev, 2015, 34: 77-81.
21
Sahara M, Santoro F, Chien KR. Programming and reprogramming a human heart cell [J]. EMBO J, 2015, 34(6): 710-738.
22
张成, 章少中, 张亚洲, 等. 诱导心脏肌成纤维细胞向心肌样细胞转分化的miRNA [J]. 中国组织工程研究, 2013, 17(45): 7924-7931.
23
Efe JA, Hilcove S, Kim J, et al. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy [J]. Nat Cell Biol, 2011, 13(3): 215-222.
24
Talkhabi M, Pahlavan S, Aghdami N, et al. Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes [J]. Biochem Biophys Res Commun, 2015, 463(4): 699-705.
25
Jayawardena T, Mirotsou M, Dzau VJ. Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs [J]. Methods Mol Biol, 2014, 1150(1150): 263-272.
26
Zhao Y, Londono P, Cao Y, et al. High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling [J]. Nat Commun, 2014, 6: 8243-8258.
27
Palazzolo G, Quattrocelli M, Toelen J, et al. Cardiac niche influences the direct reprogramming of canine fibroblasts into cardiomyocyte-like cells [J]. Stem Cell Int, 2016, 2016: 4969430.
28
Furtado MB, Costa MW, Pranoto EA, et al. Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair [J]. Circ Res, 2014, 114(9): 1422-1434.
29
Nam YJ, Lubczyk C, Bhakta M, et al. Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors [J]. Development, 2014, 141(22): 4267-4278.
30
Gherghiceanu M, Barad L, Novak A, et al. Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: Comparative ultrastructure [J]. J Cell Mol Med, 2011, 15(11): 2539-2551.
31
Ma H. In vivo cardiac reprogramming using an optimal single polycistronic construct [J]. Cardiovasc Res, 2015, 108(2): 217-229.
32
Rysä J, Tenhunen O, Serpi R, et al. GATA-4 is an angiogenic survival factor of the infarcted heart [J]. Circ Heart Fail, 2010, 3(3): 440-450.
33
Lalit PA, Salick MR, Nelson DO, et al. Lineage reprogramming of fibroblasts to proliferative induced cardiac progenitor cells by defined factors [J]. Cell Stem Cell, 2016, 18(3): 354-367.
34
Zhang Y, Cao N, Huang Y, et al. Expandable cardiovascular progenitor cells reprogrammed from fibroblasts [J]. Cell Stem Cell, 2016, 18(3): 368-381.
35
Pratico ED, Feger BJ, Watson MJ, et al. RNA-mediated reprogramming of primary adult human dermal fibroblasts into c-kit(+) cardiac progenitor cells [J]. Stem Cells Dev, 2015, 24(22): 2622-2633.
36
Gong K, Chen YF, Li P, et al. Transforming growth factor-β inhibits myocardial PPARγ expression in pressure overload-induced cardiac fibrosis and remodeling in mice [J]. J Hypertens, 2011, 29(9): 1810-1819.
37
Cunnington RH, Wang B, Ghavami S, et al. Antifibrotic properties of c-Ski and its regulation of cardiac myofibroblast phenotype and contractility [J]. Am J Physiol, 2010, 300(1): C176-186.
38
Wang Y, Aitoufella H, Herbin O, et al. TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin Ⅱ-infused mice [J]. J Clin Invest, 2010, 120(2): 422-432.
39
Arslan F, Smeets MB, Riem Vis PW, et al. Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction [J]. Circ Res, 2011, 108(5): 582-592.
40
Gonzalez-Santamaria J, Villalba M, Busnadiego O, et al. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction [J]. Cardiovasc Res, 2016, 109(1): 67-78.
41
Schuetze KB, Mckinsey TA, Long CS. Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs [J]. J Mol Cell Cardiol, 2014, 70(9): 100-107.
42
Lee CY, Burnett JC Jr. Natriuretic peptides and therapeutic applications [J]. Heart Fail Rev, 2007, 12(2): 131-142.
43
李世强, 傅向华, 刘君, 等. 静脉注射重组人脑利钠肽对急性心肌梗死伴心力衰竭患者的急性血流动力学效应的研究 [J]. 中华心血管病杂志, 2006, 34(1): 23-27.
44
Moilanen AM, Rysä J, Serpi R, et al. (Pro)renin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function [J]. PLoS One, 2012, 7(7): e41404.
45
Corinaldesi C, Luigi LD, Lenzi A, et al. Phosphodiesterase type 5 inhibitors: back and forward from cardiac indications [J]. J Endocrinol Invest, 2016, 39(2): 143-151.
46
Wang K, Zhao X, Kuang C, et al. Overexpression of SDF-1alpha enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway [J]. PLoS one, 2012, 7(9): e43922.
47
Chen Z, Zeng C, Wang WE. Progress of stem cell transplantation for treating myocardial infarction [J]. Curr Stem Cell Res Ther, 2017, 12(8): 624-636.
[1] 陈玲, 李楠, 杨建乐. 微小RNA-377-3p调控自噬改善脂多糖/D-半乳糖胺诱导的急性肝衰竭的机制研究[J]. 中华危重症医学杂志(电子版), 2023, 16(02): 89-97.
[2] 李敏, 杨凡. 肌细胞因子在儿童肥胖症患儿运动减脂中的作用研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 125-131.
[3] 李硕, 尹希, 祁连港, 王丽, 刘宗宝. 浓缩生长因子在促进失神经皮瓣术后神经再生的应用前景[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 547-551.
[4] 何雪锋, 赵世新, 李珮珊, 刘恒登, 谢举临. 卡奴卡叶提取物通过增强真皮成纤维细胞功能促进大鼠创面修复的效果观察[J]. 中华损伤与修复杂志(电子版), 2023, 18(05): 405-412.
[5] 黄瑞娟, 德奇, 巴特, 周彪. 对人脐带间充质干细胞外泌体影响热损伤人皮肤成纤维细胞迁移的分析[J]. 中华损伤与修复杂志(电子版), 2023, 18(03): 229-234.
[6] 甄妙, 李婧婷, 王鹏, 舒斌. 对表皮干细胞外泌体影响增生性瘢痕成纤维细胞作用的观察[J]. 中华损伤与修复杂志(电子版), 2023, 18(02): 134-143.
[7] 魏忠玲, 陈赟, 叶美霞, 杨珺雯, 袁竺方. 不同种类敷料治疗糖尿病足疗效比较的网状荟萃分析[J]. 中华损伤与修复杂志(电子版), 2023, 18(02): 157-165.
[8] 宫镇江, 王守一, 姚超, 庞永志, 崔婧. sticky bone混合浓缩生长因子应用于水平骨增量患者的临床效果研究[J]. 中华口腔医学研究杂志(电子版), 2023, 17(06): 430-435.
[9] 王军辉, 胡颖, 刘芳, 王飞, 陈宇江, 王小竞. 浓缩生长因子用于年轻恒牙根尖周炎再生性牙髓治疗2例及文献复习[J]. 中华口腔医学研究杂志(电子版), 2023, 17(02): 81-88.
[10] 叶晓琳, 刘云飞, 庞明泉, 王海久, 任利, 侯立朝, 于文昊, 王志鑫, 樊海宁. 肝再生细胞来源及调控机制的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 96-99.
[11] 钟文文, 李科, 刘碧好, 蔡炳, 脱颖, 叶雷, 马波, 瞿虎, 汪中扬, 王德娟, 邱剑光. 不同比例聚乳酸/丝素蛋白复合支架在兔尿道缺损修复中的疗效[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 516-522.
[12] 李颖思, 符芳, 杨昕, 邓琼, 周航, 程肯, 李东至, 廖灿. 单细胞RNA测序技术探究CCN2基因在特纳综合征胎儿颈部淋巴水囊瘤中的关键作用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(04): 220-228.
[13] 赵子祯, 严紫娟, 王家传. 脑类器官培养技术进展及其在缺血性脑卒中损伤修复中的应用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 121-128.
[14] 那迪娜·帕尔哈提, 黄陈. 肿瘤相关成纤维细胞在结直肠癌发生与发展及化疗耐药中的作用研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(03): 241-247.
[15] 郭晓磊, 李晓云, 孙嘉怿, 金乐, 郭亚娟, 史新立. 含生长因子骨移植材料的研究进展和监管现状[J]. 中华老年骨科与康复电子杂志, 2023, 09(06): 373-378.
阅读次数
全文


摘要