Article

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

Zhen-duo Zhu1,2, Mei Zhang1,2,3, Zhen Wang1,2, Chun-ru Jiang1,2, Chong-jian Huang4,5, Hui-juan Cheng1,2, Qiu-yun Guan1,2, Tian-tian Su1,2, Man-man Wang1,2, Yi Gao6, Hong-fei Wu7, Wei Wei1,2, Yong-sheng Han4,5, Qing-tong Wang1,2
1 The Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education
2 Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China
3 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China
4 Department of Emergency Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, China
5 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
6 Department of Pathology, Anhui Medical University, Hefei 230032, China
7 College of Pharmacy, Anhui University of Chinese Medicine, Anhui Key Laboratory for Research and Development of Traditional Chinese Medicine, Hefei 230038, China
Correspondence to: Yong-sheng Han: hanysh1017@126.com, Qing-tong Wang: qingtongwang@ahmu.edu.cn,
DOI: 10.1038/s41401-023-01099-2
Received: 27 December 2022
Accepted: 24 April 2023
Advance online: 2 June 2023

Abstract

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.

Keywords: cardiomyopathy; rheumatoid arthritis; collagen-induced arthritis; β-adrenergic receptor; G protein-coupled receptor kinase 2; epinephrine

Article Options

Download Citation

Cited times in Scopus