sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery.
Arterial smooth muscle cell (SMC) proliferation is thought to be an essential aspect of the development of human atherosclerotic lesions. In this study we posed the question, could a growth factor gene be transcriptionally active in atherosclerotic tissue? We found that transcripts from the sis gene, which encodes one of the two chains of platelet-derived growth factor, were present in surgically removed human carotid artery lesions at levels 5-fold greater than the low level of constitutive expression detected in normal artery. This demonstrates that a growth factor could be synthesized endogenously within human atherosclerotic lesions. Although atherosclerotic lesions are composed predominantly of SMC, large numbers of infiltrating macrophages, T cells, and endothelial cells can also be present, raising the possibility that one of these secondary cell types, rather than SMC, could be responsible for the sis transcripts. Human macrophages activated in culture contained 2- to 4-fold more sis RNA, per micrograms of total cellular RNA, than lesions, whereas T cells activated in culture did not contain significant levels. Cultured human endothelial cells expressed sis transcripts at higher levels than macrophages. Since human arterial SMC in culture express receptors for and are mitogenically responsive to platelet-derived growth factor, transcription of the sis gene by cells within lesions, whether these cells are SMC themselves, macrophages, endothelial cells, or another cell type, suggests that an autocrine and/or paracrine proliferative mechanism is important in the pathogenesis of atherosclerosis.
D001158:Arteries / Q000502:physiology*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D005796:Genes; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012313:RNA / Q000378:metabolism; D012016:Reference Values; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D012313:RNA