Elucidating the Roles of Resident Cardiac Macrophages in Post-Infarction Reperfusion Injury (Predoctoral Fellowship for Shang Yang Chen)

Project: Research project

Project Details

Description

Prompt clinical reperfusion is essential for positive outcomes of acute myocardial infarction (MI), but reperfusion itself can cause further injury to the myocardium, leading to adverse cardiac remodeling and increases the risks for heart failure in the future. It is known that blood monocytes are recruited to the myocardium upon reperfusion and drive tissue damage through secretion of pro-inflammatory cytokines. Recent studies have implicated resident cardiac macrophages as the counterpart of monocytes, actively participating in post-MI cardiac repair through efferocytosis and production of anti-inflammatory cytokines. However, there are at least three distinct macrophage populations residing in the healthy myocardium with divergent developmental (embryonic and monocytic) origins, and they seemingly possess different phagocytic and regenerative potentials. In this application, we aim to answer whether different cardiac macrophage populations contribute differentially to the pathophysiology of post-MI reperfusion injury. We propose to profile and analyze the transcriptional and epigenomic landscapes of mice cardiac macrophage populations at steady state (Aim 1) and after experimental reperfusion (Aim 2) through high-throughput sequencing assays. We have previously demonstrated the potential of using this approach to study different immune cell types. The overall hypothesis is that cardiac macrophages with embryonic origins should display distinct expression and chromatin profiles compared to those derived from monocytes during steady state, which primed for the differential response and contribution to post-MI reperfusion injury and cardiac repair. We will perform RNA-seq for gene expression, ChIP-seq for histone modifications, and ATAC-seq for chromatin accessibility. This application represents the first proposal to profile the epigenomic landscapes of cardiac macrophages, which may allow us to uncover pathways central to the mechanisms of post-MI reperfusion inju
StatusFinished
Effective start/end date3/1/1912/31/20

Funding

  • American Heart Association (19PRE34380200)

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