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

HAO Wei-Wei¹, ZHANG Su-Li¹, SUN Yan¹, BAI Li-Na¹, BIAN Jing-Wei¹, YU Hai-Cun¹, YIN Xiao-Chen¹, WANG Peng-Li¹, LIU Hui-Rong^1,2,*

¹Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China；²Beijing Key Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction, Capital Medical University, Beijing 100069, China

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 8th 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.

Key words: angiotensin II type 1 receptor autoantibody; myocardial fibrosis; cardiac fibroblasts; cardiac remodeling ; heart failure

Received: 2018-02-01　　Accepted: 2018-02-01

Corresponding author: 刘慧荣　　E-mail: liuhr2000@126.com

DOI: 10.13294/j.aps.2018.0055

Citing This Article：

HAO Wei-Wei, ZHANG Su-Li, SUN Yan, BAI Li-Na, BIAN Jing-Wei, YU Hai-Cun, YIN Xiao-Chen, WANG Peng-Li, LIU Hui-Rong. Angiotensin II type 1 receptor autoantibody induces myocardial fibrosis by activating cardiac fibroblasts. Acta Physiol Sin 2018; 70 (4): 343-353 (in Chinese with English abstract).