Effect of phenotype on the transcription of the genes for platelet-derived growth factor (PDGF) isoforms in human smooth muscle cells, monocyte-derived macrophages, and endothelial cells in vitro
1997 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 17, no 11, 2897-2903 p.Article in journal (Refereed) Published
Proliferation of arterial smooth muscle cells (ASMCs) contributes considerably to enlargement of the arterial wall during atherosclerosis. The platelet-derived growth factor (PDGF) is a well-known mitogen and chemoattractant for ASMCs. Quantitative reverse transcription-polymerase chain reaction showed that cells appearing in atherosclerotic lesions, such as ASMCs, endothelial cells, and monocytes/macrophages, expressed mRNAs for both PDGF A and B chains in vitro, with the highest expression in endothelial cells. On proliferation, ASMCs and endothelial cells upregulated PDGF A mRNA. Differentiation of macrophages increased the amount of both mRNAs. Thus, the regulation of PDGF A- and B-chain expression depends on cell types and phenotypic states of the cells, which have also been found in vivo in human atherosclerotic lesions. PDGF A can be produced as short and long isoforms. The latter binds with high affinity to glycosaminoglycans. Irrespective of phenotype, only the minor part of total PDGF A mRNA consisted of the long variant in ASMCs, while endothelial cells produced 40% of total PDGF A as the long form. The differentiation of macrophages increased the production of the long PDGF A mRNA from 10% to 40%. Thus, increasing numbers of stimulated cells in the atherosclerotic lesion may increase the transcription of PDGF isoforms, and particularly of the long PDGF A isoform. Together with increasing amounts of ASMC-derived proteoglycans in developing lesions, this may contribute to accumulation of PDGF in the arterial wall matrix, resulting in prolonged stimulation of ASMCs.
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 1997. Vol. 17, no 11, 2897-2903 p.
Differentiation, Endothelial cells, Macrophages, Platelet-derived growth factor, Smooth muscle cells
Other Basic Medicine
IdentifiersURN: urn:nbn:se:his:diva-11410ISI: A1997YL00800078PubMedID: 9409273ScopusID: 2-s2.0-0031440924OAI: oai:DiVA.org:his-11410DiVA: diva2:848238