Pro-remodeling effect of autoantibody against beta(1)-adrenoceptor on cardiomyocytes involves T cells dysfunction under the pathological condition of heart failure
机构：[a]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China首都医科大学附属安贞医院[b]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China[c]Department of Pathophysiology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China
Autoantibody against beta(1)-adrenoceptor (beta(1)-AA) has been shown to be closely linked to the aggravation of heart failure. Removal of beta(1)-AA remarkably attenuated patients' cardiac dysfunction. We found that beta(1)-AA induced rat heart failure with increased CD4(+) T cells. However, whether or not beta(1)-AA interacts with T cells isolated from heart failure patients remains unknown. Twenty-one beta(1)-AA-negative heart failure patients were divided into those taking beta-adrenergic blocker and those not. The effects of beta(1)-AA monoclonal antibodies (beta(1)-AAmAb) on T cells proliferation were detected using the CCK-8 assay. IFN-gamma and IL-4 production by human T cells were measured by after the administration of beta 1-AAmAb. The levels of cardiomyocyte apoptosis and hypertrophy were detected after co-cultured with the supernatant of T cells pre-stimulated by beta(1)-AAmAb. It was found that beta(1)-AAmAb promoted T cell proliferation via the beta 1-AR/cAMP/PKA pathway in patients who not take beta-blocker. beta(1)-AAmAb inhibited the characteristic cytokine secretion of Th1, IFN-gamma, but had no significant effect on the Th2 cytokine IL-4. Supernatant resulted from the T cells pre-treated with beta(1)-AAmAb induced cardiomyocytes remodeling, as evidenced by increased levels of cardiomyocytes apoptosis and hypertrophy. We propose that heart failure is likely to be an interference factor for Th-mediated immunity, and the presence of beta(1)-AAmAb may aggravate this effect and deteriorate concomitant inflammatory injury in cardiomyocytes, partially via beta(1)-AR/cAMP/PKA pathway. (C) 2019 Elsevier Inc. All rights reserved.
基金：
Natural Science Foundation of ChinaNational Natural Science Foundation of China [81470540]
第一作者机构：[a]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China
共同第一作者：
通讯作者：
通讯机构：[b]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China[*1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
推荐引用方式(GB/T 7714)：
Yunhui Du,Shihan Zhang,Wenjing Hao,et al.Pro-remodeling effect of autoantibody against beta(1)-adrenoceptor on cardiomyocytes involves T cells dysfunction under the pathological condition of heart failure[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2019,510(1):163-170.doi:10.1016/j.bbrc.2019.01.072.
APA：
Yunhui Du,Shihan Zhang,Wenjing Hao,Wenli Xu,Li Yan&Huirong Liu.(2019).Pro-remodeling effect of autoantibody against beta(1)-adrenoceptor on cardiomyocytes involves T cells dysfunction under the pathological condition of heart failure.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,510,(1)
MLA：
Yunhui Du,et al."Pro-remodeling effect of autoantibody against beta(1)-adrenoceptor on cardiomyocytes involves T cells dysfunction under the pathological condition of heart failure".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 510..1(2019):163-170
