PDF(Pubmed)
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.
摘要：
类风湿关节炎（RA）患者的心功能不全发生率要高得多，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RA动物模型中心脏功能的动态变化,并研究了RA诱导的心力衰竭(HF)的潜在效应因子.建立大鼠和小鼠胶原诱导的关节炎(CIA)模型。使用超声心动图和血液动力学动态监测CIA动物的心脏功能。我们表明，心脏舒张和收缩功能障碍发生在CIA动物中，并在关节炎症后持续存在，并且血清促炎细胞因子（IL-1β，TNF-α）水平降低。即使心肌病很明显，我们也没有在关节炎动物中发现动脉粥样硬化（AS）的证据。我们观察到，CIA大鼠的心脏β1AR兴奋收缩耦合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)。InCIA小鼠，用非选择性βAR阻滞剂卡维地洛（2.5mg·kg-1·d-1，持续4周）或特定的GRK2抑制剂帕罗西汀（2.5mg·kg-1·d-1，持续4周）治疗可有效挽救心脏功能。我们得出结论，CIA动物的慢性和持续的β-肾上腺素能应激是心肌病的重要原因，这可能是保护RA患者免受HF的潜在目标。
