Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall.
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.
Barrett
T B
TB
Department of Pathology, University of Washington, Seattle 98195.
Benditt
E P
EP
D000199:Actins / Q000235:genetics; D001158:Arteries / Q000166:cytology / Q000502:physiology*; D001161:Arteriosclerosis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D009693:Nucleic Acid Hybridization; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics
D000199:Actins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014841:von Willebrand Factor