Chronic β-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis
Chronic β-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis
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DOI：
10.1038/s41401-023-01099-2
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发表时间：
2023-06-02
影响因子：
8.2
通讯作者：
Wang，Qing-tong
中科院分区：
文献类型：
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作者：
Zhu，Zhen-duo;Zhang，Mei;Wang，Qing-tong
类风湿性关节炎（RA）患者心功能不全的发生率较高，尽管抗关节炎药物治疗，但仍导致RA的高死亡率。在这项研究中，我们研究了经典的RA动物模型的心功能的动态变化，并检查了RA诱导的心力衰竭（HF）的潜在效应。建立大鼠和小鼠胶原诱导性关节炎（CIA）模型。用超声心动图和血流动力学动态监测CIA动物的心功能。我们发现CIA动物出现心脏舒张和收缩功能障碍，并在关节炎症后持续存在，血清促炎细胞因子（IL-1β，TNF-α）水平降低。我们没有发现动脉粥样硬化（AS）在关节炎动物的证据，即使心肌病是显着的。我们观察到CIA大鼠心脏β 1 AR兴奋收缩偶联信号受损伴随着血液肾上腺素水平的持续升高。此外，RA患者血清肾上腺素浓度与心力衰竭标志物NT-proBNP呈正相关（r2=+0.53，P < 0.0001）。在CIA小鼠中，非选择性βAR阻断剂卡维地洛（2.5 mg·kg-1·d-1，持续4周）或特异性GRK 2抑制剂帕罗西汀（2.5 mg·kg-1·d-1，持续4周）有效地挽救了心脏功能。我们的结论是，慢性和持续的β-肾上腺素能应激在CIA动物是一个显着的贡献者心肌病，这可能是一个潜在的目标，保护RA患者对HF。
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.