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Updated: Aug 29, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Macrophage Rmp Ameliorates Myocardial Infarction by Modulating Macrophage Polarization in Mice
Jian Zhang1, Zongtao Yin1, Liming Yu1
1Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning, China.
Background:
Inflammation plays important roles during myocardial infarction (MI). Macrophage polarization is a major factor that drives the inflammatory process. Our previous study found that RNA polymerase II subunit 5-mediating protein (RMP) knockout in cardiomyocytes caused heart failure by impairing mitochondrial structure and function. However, whether macrophage RMP plays a role in MI has not been investigated.
Methods:
Macrophage RMP-knockout in combination with a mouse model of MI was used to study the function of macrophage RMP in MI. Next, we modified bone marrow-derived macrophages (BMDMs) by plasmid transfection, and the BMDMs were administered to LysM-Cre/DTR mice by tail vein injection. Immunoblotting and immunofluorescence were used to detect macrophage polarization, fibrosis, angiogenesis, and the p38 signaling pathway in each group.
Results:
Macrophage RMP deficiency aggravates cardiac dysfunction, promotes M1 polarization, and inhibits angiogenesis after MI. However, RMP overexpression in macrophages promotes M2 polarization and angiogenesis after MI. Mechanistically, we found that RMP regulates macrophage polarization through the heat shock protein 90- (HSP90-) p38 signaling pathway.
Conclusions:
Macrophage RMP plays a significant role in MI, likely by regulating macrophage polarization via the HSP90-p38 signaling pathway.
Insights
Macrophage RNA polymerase II subunit 5-mediating protein (RMP) deficiency worsens heart attack outcomes by promoting inflammation. RMP regulates this process via the HSP90-p38 pathway, impacting macrophage polarization and healing.
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.
