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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2897-2903.)
© 1997 American Heart Association, Inc.

Articles

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

Alexandra Krettek; Gunnar Fager; Helena Lindmark; Carolina Simonson; ; Florentyna Lustig

From the Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.

Correspondence to Alexandra Krettek, Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail alexandra.krettek{at}wlab.wall.gu.se

Abstract 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.

Key Words: smooth muscle cells • macrophages • endothelial cells • differentiation • platelet-derived growth factor

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