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Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Expression of heregulin in human coronary atherosclerotic lesions
Dimitrios Panutsopulos1, Dimitrios L Arvanitis, Christos Tsatsanis
1Laboratory of Virology, Medical School, University of Crete, Heraklion, Greece.
Insights
Heregulin (HRG) is overexpressed in human coronary artery disease lesions, particularly in macrophages. HRG promotes the expression of angiogenetic factors like CYR61, suggesting a role in atherosclerotic plaque expansion.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Immunology
Background:
- Atherosclerosis involves endothelial cells, macrophages, and smooth muscle cells producing growth and inflammatory factors.
- Understanding the molecular mechanisms driving atherosclerotic lesion progression is crucial.
Purpose of the Study:
- To investigate the association between heregulin (HRG) and human coronary artery disease.
- To explore HRG's role in the cellular components of atherosclerotic plaques.
Main Methods:
- Analysis of 26 human coronary artery segments for HRG and CYR61 expression.
- In vitro studies using human endothelial cells (EA.hy926) and primary human macrophages.
Main Results:
- Heregulin (HRG) was significantly overexpressed in atherosclerotic lesions, increasing with lesion stage.
- HRG expression was primarily localized to macrophages within the intima.
- HRG induced the expression of cysteine-rich 61 (CYR61) and vascular endothelial growth factor (VEGF) in endothelial cells.
Conclusions:
- Heregulin (HRG) plays a significant role in the development and expansion of atherosclerotic plaques.
- HRG may locally regulate the expression of the angiogenetic factor CYR61 in coronary artery disease.
Background:
Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease.
Methods:
Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA.hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors.
Results:
We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in breast cancer epithelial cells. CYR61 was expressed in both normal and atheromatic specimens, but its expression was significantly enhanced in macrophages of the intima. Activation of primary human macrophages results in increased expression of both HRG and CYR61. In addition, studies in endothelial cells where no endogenous HRG is present showed that HRG induces expression of CYR61 and secretion of VEGF.
Conclusions:
HRG may, therefore, play an important role in the development of coronary artery disease and the expansion of the atherosclerotic plaque and may locally regulate the expression of the angiogenetic factor CYR61.
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