机构：[1]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China首都医科大学附属安贞医院[2]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China[3]Department of Basic Medical Sciences, Yanjing Medical College, Capital Medical University, Beijing, China[4]Zhengzhou Central Hospital affiliated of Zhengzhou University, Henan Province, China
Background Autoantibodies against the second extracellular loop of the β1-adrenoceptor (β1- AA ) act similarly to agonist of β1-adrenergic receptor, which plays an important role in the pathophysiological characteristics of ventricular remodeling. Recently, considerable lines of evidence have suggested that CTRP9 (C1q tumor necrosis factor-related protein 9) is a potent cardioprotective cardiokine and protects the heart from ventricular remodeling. The aim of this study was to determine the role of CTRP 9 in ventricular remodeling induced by β1- AA . Methods and Results Blood samples were collected from 131 patients with coronary heart disease and 131 healthy subjects. The serum levels of β1- AA and CTRP 9 were detected using ELISA . The results revealed that CTRP 9 levels in β1- AA -positive patients were lower than those in β1- AA -negative patients, and serum CTRP 9 concentrations were inversely correlated with β1- AA . β1- AA monoclonal antibodies (β1- AA mAbs) were administered in mice with and without rAAV 9- cTnT -Full Ctrp9- FLAG virus for 8 weeks. Reverse transcription-polymerase chain reaction/Western analysis showed that cardiomyocyte CTRP 9 expression was significantly reduced in β1- AA mAb-treated mice. Moreover, compared with the β1- AA mAb alone group, cardiac-specific CTRP 9 overexpression improved cardiac function, attenuated adverse remodeling, and ameliorated cardiomyocyte apoptosis and fibrosis. Mechanistic studies demonstrated that CTRP 9 overexpression decreased the levels of G-protein-coupled receptor kinase 2 and promoted the activation of AMP-dependent kinase pathway. However, cardiac-specific overexpression of CTRP 9 had no effect on the levels of cAMP and protein kinase A activity elevated by β1-AAmAb. Conclusions This study provides the first evidence that the long-term existence of β1- AA mAb suppresses cardiac CTRP 9 expression and exaggerates cardiac remodeling, suggesting that CTRP 9 may be a novel therapeutic target against pathologic remodeling in β1- AA -positive patients with coronary heart disease.
第一作者机构：[1]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[3]Department of Basic Medical Sciences, Yanjing Medical College, Capital Medical University, Beijing, China[4]Zhengzhou Central Hospital affiliated of Zhengzhou University, Henan Province, China[*1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.[*2]Department of Basic Medical Sciences, Yanjing Medical College, Capital Medical University, Beijing, China.
推荐引用方式(GB/T 7714)：
Yunhui Du ,Shihan Zhang ,Haicun Yu ,et al.Autoantibodies Against β1-Adrenoceptor Exaggerated Ventricular Remodeling by Inhibiting CTRP9 Expression.[J].Journal of the American Heart Association.2019,8(4):e010475.doi:10.1161/JAHA.118.010475.
APA：
Yunhui Du,,Shihan Zhang,,Haicun Yu,,Ye Wu, MD,,Ning Cao,...&Huirong Liu,.(2019).Autoantibodies Against β1-Adrenoceptor Exaggerated Ventricular Remodeling by Inhibiting CTRP9 Expression..Journal of the American Heart Association,8,(4)
MLA：
Yunhui Du,,et al."Autoantibodies Against β1-Adrenoceptor Exaggerated Ventricular Remodeling by Inhibiting CTRP9 Expression.".Journal of the American Heart Association 8..4(2019):e010475
医学