心力衰竭（心衰）是目前威胁人类健康的重大疾病，而G蛋白偶联受体（GPCR）是心衰治疗的重要药物靶点。近年来的研究发现GPCR信号转导除G蛋白介导的经典信号通路之外还有G蛋白非依赖，beta-arrestin（b-arr）依赖的偏向性信号转导模式。b-arr1和b-arr2是心脏中最主要的b-arr亚型，但是目前对它们在心脏中的非受体依赖的功能还不清楚。本课题希望研究b-arr1和b-arr2在多种原因（包括心脏缺血/再灌损伤和心肌肥厚）引起的心脏损伤和心衰中的作用，尤其是其非受体依赖的功能，并且深入探讨其作用机制。本课题旨在增进对GPCR偏向性信号转导的认识、拓展GPCR理论，为心肌损伤和心衰的预防和治疗提供新靶点和新策略。

Heart failure (HF) is a global threat to human health. G protein-coupled receptor (GPCR) is the most important class of drug targets for the treatment of HF. In addition to the classic G protein-dependent pathway, G protein-independent, b-arrestin-meditated biased signaling has been recently identified. In cardiomyocytes, b-arrestin1 and b-arrestin2 are the major isoforms, but their functions, especially receptor-independent functions, in the heart remain largely elusive. Here, we seek to investigate (1) receptor-independent biological functions of b-arrestin1 and b-arrestin2 in the heart, (2) to determine their potential involvements in cardiac injury and HF induced by multiple insults (ischemia/reperfusion and cardiac hypertrophy), and (3) to explore the mechanisms of action. The proposed study will not only deepen our understanding of the GPCR biased singling, but also provide novel therapeutic targets for HF treatment.