Macrophage Rmp Ameliorates Myocardial Infarction by Modulating Macrophage Polarization in Mice

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Inflammation is critical in myocardial infarction (MI).
• Macrophage polarization significantly influences the inflammatory response during MI.
• Previous research linked cardiomyocyte RNA polymerase II subunit 5-mediating protein (RMP) knockout to heart failure, but macrophage RMP's role in MI remained unknown.

Purpose of the Study:

• To investigate the function of macrophage RMP in myocardial infarction (MI).
• To determine the underlying molecular mechanisms by which macrophage RMP influences MI progression.

Main Methods:

• Utilized a mouse model of MI with macrophage-specific RMP knockout.
• Employed bone marrow-derived macrophages (BMDMs) modified via plasmid transfection and administered to LysM-Cre/DTR mice.
• Assessed macrophage polarization, fibrosis, angiogenesis, and the p38 signaling pathway using immunoblotting and immunofluorescence.

Main Results:

• Macrophage RMP deficiency exacerbated cardiac dysfunction and promoted M1 polarization while inhibiting angiogenesis post-MI.
• Conversely, RMP overexpression in macrophages enhanced M2 polarization and promoted angiogenesis.
• RMP was found to regulate macrophage polarization through the heat shock protein 90 (HSP90)-p38 signaling pathway.

Conclusions:

• Macrophage RMP plays a crucial role in myocardial infarction.
• RMP regulates macrophage polarization via the HSP90-p38 signaling pathway, impacting MI outcomes.
• Targeting macrophage RMP presents a potential therapeutic strategy for MI.