# Efferocytosis in myocardial infarction: the regulatory core from inflammation resolution to cardiac repair

## TL;DR

This paper reviews how the process of efferocytosis helps resolve inflammation and promote heart repair after a heart attack, and how targeting this process could lead to new therapies.

## Contribution

The paper provides a systematic review of efferocytosis's regulatory role in post-MI inflammation resolution and cardiac repair, emphasizing context-dependent therapeutic approaches.

## Key findings

- Efferocytosis orchestrates the post-MI immune environment through spatiotemporal regulation.
- Dysfunction in efferocytosis leads to sustained inflammation and heart failure.
- Therapeutic strategies include disabling 'don't-eat-me' signals and reprogramming the immune microenvironment.

## Abstract

Effective tissue repair after acute myocardial infarction (MI) critically depends on the timely and orderly resolution of inflammation. This review systematically elaborates the core “directorial” role of efferocytosis—the immunologically silent clearance of apoptotic cells—which orchestrates the post-MI immune microenvironment from inflammation to repair through precise spatiotemporal regulation. We dissect its complete molecular program, from “find-me/eat-me” signals and TAM-TIM receptor synergy to metabolic-transcriptional reprogramming that drives repair. A key focus is how efferocytic dysfunction (e.g., MerTK cleavage, CD47 upregulation, Lgmn blockade) triggers a self-perpetuating vicious cycle of failed clearance, sustained inflammation, and repair collapse, leading to adverse remodeling and heart failure. Critically, we highlight the context-dependent duality of key molecules, emphasizing that therapeutic success requires restoring physiological balance rather than maximal pathway activation. Building on this mechanistic understanding, we review multi-dimensional strategies—disabling “don’t-eat-me” signals, enhancing degradation capacity, and reprogramming the immune microenvironment—while critically analyzing translational challenges. Finally, we envision a paradigm shift toward spatially targeted, temporally precise interventions that actively guide repair, laying a theoretical foundation for innovative efferocytosis-directed therapies.