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

Proliferation of arterial smooth muscle cells (ASMCs) contributes cons iderably to enlargement of the arterial wall during atherosclerosis. T he platelet-derived growth factor (PDGF) is a well-known mitogen and c hemoattractant for ASMCs. Quantitative reverse transcription-polymeras e chain reaction showed that cells appearing in atherosclerotic lesion s, such as ASMCs, endothelial cells, and monocytes/macrophages, expres sed mRNAs for both PDGF A and B chains in vitro, with the highest expr ession in endothelial cells. On proliferation, ASMCs and endothelial c ells 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. P DGF A can be produced as short and long isoforms. The latter binds wit h 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 lon g form. The differentiation of macrophages increased the production of the long PDGF A mRNA from 10% to 40%. Thus, increasing numbers of sti mulated cells in the atherosclerotic lesion may increase the transcrip tion of PDGF isoforms, and particularly of the long PDGF A isoform. To gether with increasing amounts of ASMC-derived-proteoglycans in develo ping lesions, this may contribute to accumulation of PDGF in the arter ial wall matrix, resulting in prolonged stimulation of ASMCs.