Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair.

Area of Science:

• Immunology and Cardiovascular Science
• Macrophage Biology and Systemic Trauma Response

Background:

• Acute myocardial infarction (AMI) triggers a systemic trauma response affecting the entire body, including blood composition.
• Macrophages are crucial for tissue repair and their role in sensing and responding to the AMI systemic environment is investigated.

Purpose of the Study:

• To determine if macrophages can sense and respond to serum changes induced by AMI.
• To identify molecular signatures and gene networks associated with AMI in macrophages.
• To explore therapeutic targets for mitigating detrimental macrophage imprinting during AMI.

Main Methods:

• Exposure of human monocyte-derived macrophages to serum from AMI patients or healthy controls.
• Transcriptional and multiparameter functional screening of macrophages.
• Network-guided data interpretation, drug repurposing, and validation in independent cohorts and public datasets.

Main Results:

• AMI serum induced a distinct macrophage signature characterized by enhanced debris cleaning, mitosis, and immune pathways.
• Identification of gene networks linked to AMI and poor clinical prognosis.
• Prostaglandin E2 (PGE2) signaling emerged as a key target for intervention in macrophage imprinting.

Conclusions:

• Macrophages undergo significant reprogramming in response to the AMI systemic environment, influencing patient prognosis.
• Targeting PGE2 signaling offers a potential strategy for clinical intervention in AMI healing.
• Findings provide new avenues for risk management in cardiovascular disease.