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.
Subject(s)
Autoantibodies/adverse effects , Fibroblasts/pathology , Heart Failure/physiopathology , Myocardium/pathology , Receptor, Angiotensin, Type 1/immunology , Animals , Cardiomyopathies/physiopathology , Collagen Type I/metabolism , Echocardiography , Fibrosis , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Myocytes, Cardiac/pathology , RatsABSTRACT
The complement C1q/TNF related protein (CTRP) family is rapidly growing and currently comprises 15 members. Although CTRP proteins share a common structure composed of four distinct domains: a signal peptide at the N terminus, a short variable region, a collagenous domain, and a C-terminal globular domain, which is homologous to adiponectin, each CTRP has a unique tissue expression profile and varied function. In this review we focus on the biochemistry and pleiotropic functions of CTRPs as new molecular mediators regulating cardiovascular metabolic disorders and its related risk factors diseases.
