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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Macrophage mediators and mechanisms in cardiovascular disease
Patrik Schelemei1,2, Elena Wagner1,2, Felix Simon Ruben Picard1,2
1University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, Cologne, Germany.
Insights
Macrophages are key in cardiovascular diseases like atherosclerosis and myocardial infarction (MI). Understanding their diverse roles in the heart and aorta offers new therapeutic targets for these conditions.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Biology
Background:
- Macrophages are central to cardiovascular diseases (CVD) such as atherosclerosis and myocardial infarction (MI).
- Atherosclerosis involves cholesterol buildup, inflammation, and plaque formation, while MI results from blocked blood flow to the heart.
- Inflammation, significantly mediated by macrophages, is a critical factor in both conditions.
Purpose of the Study:
- To compare and contrast macrophage populations in the heart and aorta.
- To analyze macrophage diversity, origin, and function in both steady-state and disease conditions (atherosclerosis and MI).
- To identify key markers, mediators, and functional states of macrophage subpopulations involved in CVD.
Main Methods:
- Integrative single-cell analysis of macrophage populations in murine and human atherosclerosis models.
- Examination of macrophages in experimental myocardial infarction models.
- Comparative analysis of macrophage characteristics in the aorta and heart.
Main Results:
- Significant overlap exists in the origin, diversity, and function of macrophages in the aorta and heart during atherosclerosis and MI.
- Specific differences and commonalities in macrophage subpopulations were identified between the heart and aorta.
- Macrophage heterogeneity is crucial in the pathogenesis of CVD.
Conclusions:
- Macrophages exhibit distinct yet overlapping characteristics in the heart and aorta during cardiovascular disease.
- A deeper understanding of macrophage ontogeny and heterogeneity is essential for developing novel anti-inflammatory treatments for CVD.
- Targeting macrophage biology presents promising therapeutic avenues for cardiovascular diseases.
Abstract:
Macrophages are major players in myocardial infarction (MI) and atherosclerosis, two major cardiovascular diseases (CVD). Atherosclerosis is caused by the buildup of cholesterol-rich lipoproteins in blood vessels, causing inflammation, vascular injury, and plaque formation. Plaque rupture or erosion can cause thrombus formation resulting in inadequate blood flow to the heart muscle and MI. Inflammation, particularly driven by macrophages, plays a central role in both atherosclerosis and MI. Recent integrative approaches of single-cell analysis-based classifications in both murine and human atherosclerosis as well as experimental MI showed overlap in origin, diversity, and function of macrophages in the aorta and the heart. We here discuss differences and communalities between macrophages in the heart and aorta at steady state and in atherosclerosis or upon MI. We focus on markers, mediators, and functional states of macrophage subpopulations. Recent trials testing anti-inflammatory agents show a major benefit in reducing the inflammatory burden of CVD patients, but highlight a necessity for a broader understanding of immune cell ontogeny and heterogeneity in CVD. The novel insights into macrophage biology in CVD represent exciting opportunities for the development of novel treatment strategies against CVD.
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