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Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall
1Department of Pathology, University of Washington, Seattle 98195.
Insights
Platelet-derived growth factor (PDGF) genes are expressed in human arteries. PDGF-A is linked to smooth muscle cells, while PDGF-B is linked to macrophages in atherosclerotic plaques, suggesting a non-proliferative role.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Atherosclerosis Research
Background:
- Platelet-derived growth factor (PDGF) is implicated in atherogenesis.
- PDGF-B mRNA is present in human atherosclerotic plaques.
- Macrophages, endothelial cells, and smooth muscle cells can express PDGF genes, but the specific cell types were unclear.
Purpose of the Study:
- To investigate the expression of PDGF-A and PDGF-B in atherosclerotic plaques and normal arteries.
- To identify the specific cell types responsible for PDGF gene expression in these tissues.
Main Methods:
- Assaying PDGF-A and -B mRNA levels in dissected carotid atherosclerotic plaques and normal artery.
- Rehybridizing blots with cell type-specific markers: fms (macrophages), von Willebrand factor (endothelial cells), and smooth muscle alpha-actin (smooth muscle cells).
Main Results:
- In plaques, PDGF-A expression correlated with smooth muscle actin (smooth muscle cells), and PDGF-B expression correlated with fms (macrophages).
- In normal arteries, PDGF-A expression was high in the media (smooth muscle cells), and PDGF-B expression was high in the adventitia.
- Both PDGF genes were transcribed in normal arteries with low cell turnover.
Conclusions:
- PDGF-A and PDGF-B gene expression occurs in specific cell types within normal and atherosclerotic arteries.
- PDGF gene expression in normal arteries suggests a nonmitogenic, maintenance function.
- These findings propose a potential non-proliferative role for PDGF in arterial tissue and plaque development.
Abstract:
We previously demonstrated that the B chain of platelet-derived growth factor (PDGF-B) is transcribed in human atherosclerotic plaques, indicating that production of growth factors within plaques could occur during atherogenesis. However, since atherosclerotic plaques are composed of several cell types and three of these--macrophages, endothelial cells, and smooth muscle cells--can express the PDGF genes, the cell type responsible for PDGF gene expression was not clear. In the present study we explore further the expression of PDGF-A and -B and identify transcriptionally active cell types. We assayed PDGF-A and -B mRNA levels in dissected fractions of carotid atherosclerotic plaques and normal artery and then sequentially rehybridized these blots with three cDNA probes that recognize cell type-specific markers: fms for macrophages, von Willebrand factor for endothelial cells, and smooth muscle alpha-actin for smooth muscle cells. In plaques, PDGF-A expression correlated with smooth muscle actin; PDGF-B expression correlated strongly with fms. PDGF-A expression correlated with smooth muscle actin. In normal vessel wall, PDGF-A expression was high in the media and again correlated with smooth muscle actin, whereas PDGF-B expression was high in the adventitia. Since transcripts from both PDGF genes are found in normal artery where cell turnover is very low, we suggest that PDGF gene expression does not necessarily function to produce smooth muscle cell proliferation. We propose that these genes may have an important nonmitogenic, maintenance function in normal arterial tissue and in the atherosclerotic plaque.