Chronic β-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis  

作　　者：Zhen-duo Zhu Mei Zhang Zhen Wang Chun-ru Jiang Chong-jian Huang Hui-juan Cheng Qiu-yun Guan Tian-tian Su Man-man Wang Yi Gao Hong-fei Wu Wei Wei Yong-sheng Han Qing-tong Wang 

机构地区：[1]The Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei,230032,China [2]Hefei Cancer Hospital,Chinese Academy of Sciences,Hefei,230031,China [3]Department of Emergency Medicine,Anhui Provincial Hospital Affiliated to Anhui Medical University,Hefei,230001,China [4]Department of Emergency Medicine,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230001,China [5]Department of Pathology,Anhui Medical University,Hefei,230032,China [6]College of Pharmacy,Anhui University of Chinese Medicine,Anhui Key Laboratory for Research and Development of Traditional Chinese Medicine,Hefei,230038,China

出　　处：《Acta Pharmacologica Sinica》2023年第10期1989-2003,共15页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81973314,81202541,and 81973332);the Anhui Provincial Natural Science Foundation for Distinguished Young Scholars(1808085J28);Collaborative Innovation Project of Key Scientific Research Platform in Anhui Universities(GXXT-2020-066);Anhui Provincial Key R&D Programs(2022e07020042);Program for Upgrading Scientific Research Level of Anhui Medical University(2019xkjT008);Academic Funding for Top-notch Talents in University Disciplines(Majors)of Anhui Province(gxbjZD2021047).

摘　　要：Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1β, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac β1AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r2 = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective βAR blocker carvedilol (2.5 mg·kg^(−1)·d^(−1), for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg^(−1)·d^(−1), for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent β-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF.

关 键 词：CARDIOMYOPATHY rheumatoid arthritis collagen-induced arthritis β-adrenergic receptor G protein-coupled receptor kinase 2 EPINEPHRINE 

分 类 号：R965[医药卫生—药理学]