Investigating the Role of AIMP2 in Cardiac Stress Responses

Brown University, Providence RI

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Cardiovascular disease is the leading cause of mortality worldwide, driven by factors such as hypertension, myocardial infarction, and genetic predispositions. Despite its prevalence, the molecular mechanisms underlying cardiac stress responses remain poorly understood. AIMP2, a core component of the multisynthetase complex (MSC), is implicated in protein synthesis regulation and cellular stress responses, but its role in maintaining cardiac homeostasis has not been elucidated. This project investigates the hypothesis that AIMP2 supports adaptive cardiac responses to stress by stabilizing MSC components and regulating protein synthesis. Aim 1 will assess the impact of AIMP2 on cardiac function through gain- and loss-of-function approaches, utilizing cardiomyocyte-specific AIMP2 knockout (AIMP2-cKO) mice and stress-induced rescue experiments. Aim 2 will explore the mechanistic role of AIMP2 in protein synthesis regulation, focusing on its influence on MSC stability, protein synthesis during cardiac stress, and functional rescue experiments in AIMP2-deficient cells. By integrating in vivo and ex vivo approaches, this research will provide critical insights into how AIMP2 modulates cardiac stress responses. The findings could uncover novel therapeutic strategies to mitigate heart disease progression by targeting the MSC and its regulatory components. The project will be conducted in the laboratory of Dr. Federica Accornero, a leader in post-transcriptional regulation of cardiac remodeling, providing a robust training environment in this emerging area of cardiac biology.