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Angiotensin Ⅱ type 1 receptor autoantibody induces myocardial fibrosis by activating cardiac fibroblasts

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Author:: No author available

Journal Title:: Acta Physiologica Sinica

Issue:: 4

DOI:: 10.13294/j.aps.2018.0055

Key Word:: 血管紧张素Ⅱ-1型受体自身抗体;心肌纤维化;心肌成纤维细胞;心脏重构;心功能不全;angiotensin Ⅱ type 1 receptor autoantibody;myocardial fibrosis;cardiac fibroblasts;cardiac remodeling;heart failure

Abstract： Myocardial fibrosis (MF) is an important pathological process of cardiac remodeling in patients with heart failure; however its etiology has not been clear. It has been known that the angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) is present in patients with heart failure, but it is unclear whether this antibody directly causes MF. In this study, we investigated the role of AT1-AA in MF and its effects on cardiac fibroblasts (CFs). The AT1-AA positive rat model was established by active immunization method, and the measurement of indexes were made in the 8 th week after active immunity. The results of heart echocardiography showed that the cardiac systolic and diastolic functions of AT1-AA positive rats were impaired with reduced left ventricular wall thickness and enlarged heart chambers. HE staining results showed that the myocardial fibers were disorganized and ruptured, and Masson staining revealed that the area of collagen fibers around the myocardium and coronary arteries was significantly increased in AT1-AA positive group compared with that of the control group (P〈0.05). Moreover, primary CFs isolated from neonatal rats were cultured and treated with AT1-AA for 48 h. CCK-8 and immunofluorescence staining results showed that AT1-AA enhanced proliferation rate of CFs (P〈0.001), and Western blot results showed that AT1-AA significantly increased expressions of collagen I (Col I), Col III, matrix metalloproteinase-2 (MMP-2) and MMP-9 in CFs (all P〈0.05). Taken together, these results suggest that AT1-AA may induce MF and cardiac dysfunction via activating CFs.

Reference

[1]刘虹,杨宇,陈珑珑.AT1-受体自身抗体与原发性高血压的关系[J].2003,(3).
[2]刘忠保,张苏丽,赵荣瑞.血管紧张素Ⅱ-1型受体抗体的制备及其生物效应检测[J].2010,(12).
[3]仇燕,朱峰,廖玉华,等.高血压病患者血清抗血管紧张素Ⅱ1型受体自身抗体与心脏重构的相关分析[J].2007,(12).
[4]Zhen-Zhou, Zhang,Yu-Wen, Cheng,Hai-Yan, Jin,etc.The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by targeting AMPK-ACE2 signaling.[J].2017,8(42).
[5]Toru, Shimizu,Nikhil, Narang,Phetcharat, Chen,etc.Fibroblast deletion of ROCK2 attenuates cardiac hypertrophy, fibrosis, and diastolic dysfunction.[J].2017,2(13).
[6]Wallukat,G.,Schimke,I..Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases[J].2014,36(3).
[7]Duprez DA.Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review.[J].2006,24(6).
[8]Li, Li,Kelsey R, Bounds,Piyali, Chatterjee,etc.MicroRNA-130a, a Potential Antifibrotic Target in Cardiac Fibrosis.[J].2017,6(11).
[9]Choi, Sun Young,Park, Jong Sung,Roh, Mee Sook,etc.Inhibition of Angiotensin II-Induced Cardiac Fibrosis by Atorvastatin in Adiponectin Knockout Mice[J].2017,52(5).
[10]Bowers SL,Baudino TA,Souders CA.Cardiac fibroblast: the renaissance cell.[J].2009,105(12).
[11]Straubinger, Julia,Schoettle, Verena,Friebe, Andreas,etc.Sildenafil Does Not Prevent Heart Hypertrophy and Fibrosis Induced by Cardiomyocyte Angiotensin II Type 1 Receptor Signaling[J].2015,354(3).
[12]Z-C, Wang,J, Qi,L-M, Liu,etc.Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells.[J].2017,21(5).
[13]Wallukat G,Homuth V,Fischer T,etc.Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor.[J].1999,103(7).
[14]Fangying, Yan,Xiaobin, Guo,Xiaolan, Shan,etc.SIRT3 inhibits Ang II-induced transdifferentiation of cardiac fibroblasts through β-catenin/PPAR-γ signaling.[J].2017,(Spec ).
[15]Cunningham, Mark W., Jr.,Williams, Jan M.,Amaral, Lorena,etc.Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance Angiotensin II-Induced Renal Vascular Sensitivity and Reduce Renal Function During Pregnancy[J].2016,68(5).
[16].Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.[J].2017,11(Spec).
[17]Herlitz H,Schulze W,Wallukat G,etc.Agonist-like activity of antibodies to angiotensin II receptor subtype 1 (AT1) from rats immunized with AT1 receptor peptide.[J].1999,8(5).
[18]Vivek P. Singh,Kenneth M. Baker,Rajesh Kumar.Activation of the intracellular renin-angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production[J].2008,294(4 Pt.2).
[19]Caroline Bonnans,Jonathan Chou,Zena Werb.Remodelling the extracellular matrix in development and disease.[J].2014,15(12).
[20]Travers, Joshua G.,Kamal, Fadia A.,Robbins, Jeffrey,etc.Cardiac Fibrosis The Fibroblast Awakens[J].2016,118(6).
[21]Zhai P..Cardiac-specific overexpression of AT1 receptor mutant lacking G\u00a0q\/G\u00a0i coupling causes hypertrophy and bradycardia in transgenic mice[J].2005.
[22]Chen, Chao,Ponnusamy, Murugavel,Liu, Cuiyun,etc.MicroRNA as a Therapeutic Target in Cardiac Remodeling.[J].2017.
[23]金珠,王瑾,张文慧,等.AT1受体抗体对大鼠心肌结构和功能的影响[J].2010,(3).
[24]Drinkhill MJ,Sedo A,Ainscough JF.Angiotensin II type-1 receptor activation in the adult heart causes blood pressure-independent hypertrophy and cardiac dysfunction.[J].2009,81(3).
[25]V J, Dzau,T, Brody,K E, Ellison,etc.Tissue-specific regulation of renin expression in the mouse.[J].1987,9.
[26]ZHU Jin,Jin Wang,Wenhui Zhang,etc.Changes in cardiac structure and function in rats immunized by angiotensin type 1 receptor peptides[J].2011,(12).
[27]Li, Yulin,Li, Zhenya,Zhang, Congcong,etc.Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling[J].2017,135(21).
[28].Synergic and antagonistic relationship between MMP-2 and MMP-9 with fibrosis and inflammation in Chagas' cardiomyopathy[J].2017,39(8).
[29]Ping Kong,Panagiota Christia,Nikolaos G. Frangogiannis.The pathogenesis of cardiac fibrosis[J].2014,71(4).
[30]B, Zelezná,L, Veselsky,J, Velek,etc.Influence of active immunization against angiotensin AT1 or AT2 receptor on hypertension development in young and adult SHR.[J].1999,48.