心率是心血管疾病的晴雨表。心率的管理显著改善心血管疾病的预后。我们前期研究发现，心率在急性病毒性心肌炎（VMC）中介导促炎作用，心率增快，炎症反应增强，死亡率增加，无论采用β受体阻断剂还是单纯减慢心率药物均可以降低急性VMC小鼠心肌炎症反应。然而，心率的管理能否延缓VMC向扩张型心肌病（DCM）的演变尚未见报道。申请者发现，心率降低后可抑制多种促炎因子的表达，而这些炎症因子与VMC心肌纤维化相关，这些启示我们心率降低后很可能通过调控炎症因子的表达改善心肌纤维化，从而阻止VMC演变成DCM。本项目以慢性VMC小鼠为研究对象，从降低/增加小鼠心率着手，观察心率降低或增加后对VMC向DCM转化的作用，解析其抗心肌纤维化的下游信号转导机制。本项目最大特色是将VMC演变成DCM的机制与心率相联系。开展此项研究，不仅对VMC演变成DCM的发生发展机制提供新认识，而且还可能对VMC的治疗提供崭新的思路。

It is well established that increased heart rate is a risk factor for the development of cardiovascular events. Heart rate-controlling treatments exert several beneficial effects. We have found that increased heart rate is associated with systemic inflammation, leads to severe inflammatory injury and increases mortality in acute myocarditis, and both β-blockade and pure bradycardic agent significantly reduced the myocardial inflammation in murine acute viral myocarditis. However, the effects of heart rate reduction on the prevention of progression from viral myocarditis to dilated cardiomyopathy are unknown. Our previous studies have demonstrated that heart rate-lowering treatments significantly downregulated the expression of proinflammatory cytokines in acute myocarditis, which were associated with myocardial fibrosis and remolding. Hence, we postulate that heart-rate-reducing drugs might prevent progression from viral myocarditis to dilated cardiomyopathy by inhibiting myocardial inflammation and fibrosis and remolding. In the present study, we will investigate whether heart-rate-reducing drugs attenuates inflammation and prevents progression from viral myocarditis to dilated cardiomyopathy in mice with chronic viral myocarditis induced by coxsackievirus B3. Cardiac size and function, inflammatory cytokines, myocardial fibrosis, MAPK protein expression within the myocardium will be determined using quantitative PCR. The most novel insight of the study is that heart rate might be associated with the progression from viral myocarditis to dilated cardiomyopathy. The study will help elucidate the novel mechanism involved in the progression from viral myocarditis to dilated cardiomyopathy, and open new possibilities in the therapeutic management of viral myocarditis.