致心律失常性右室性心肌病（Arrhythmogenic right ventricular cardiomyopathy, ARVC）是一类以恶性室性心律失常和心源性猝死为主要临床表现的遗传性心肌病，其特征性病理改变为弥散性或节段性的心肌纤维脂肪替代，目前尚无有效的生物标志物对患者进行危险分层及预后评估。本课题组最新的研究发现血浆酮体β-羟基丁酸（β-hydroxybutyrate，β-OHB）含量在ARVC发生发展过程中呈现疾病进程依赖性的上升趋势，且能高度预测患者的心脏不良事件（ROC AUC=0.826, p=0.008)；本项目将在国际上首次揭示ARVC疾病进程中酮体的表观遗传学调控作用及其功能，通过细胞动物模型研究β-OHB在疾病病理发生发展中作用（病理机制及干预研究），从而深入研究β-OHB对ARVC患者的风险预测及其致病机制、寻找其可能的生物学靶点

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which pathological characteristics were ventricular myocytes loss and fibrofatty replacement. And so far, there is no effective treatment to intervene in ARVC pathological process. Recent studies of our research group have shown that plasma β-hydroxybutyrate (β-OHB) hold an upward trend corresponding with the development of ARVC. And it can predict adverse cardiac events of patients (ROC AUC=0.826, p=0.008) (under review). This project will firstly reveal the epigenetics function of β-OHB in the course of ARVC. By animal models of ARVC (DSP mice) and iPSCs, we studied on the role of β-OHB in the pathogenesis and development of ARVC. It will provide a new perspective for the ARVC disease mechanism and the experimental evidence for new drug target for prevention and treatment for ARVC in clinic.