Induction of platelet-derived growth factor chain A gene expression in human smooth muscle cells by oxidized low density lipoproteins.
Abnormal proliferation of vascular smooth muscle cells is a key event in the formation of atherosclerotic plaques in humans. It has been suggested that modulation of platelet derived growth factor chain A (PDGF-A) gene expression may contribute to atherosclerosis. Using an 'in situ hybridization' technique the present study shows that the presence of low density lipoproteins induces an eight fold increased expression of the transforming gene PDGF-A in human smooth muscle cells. The influence on PDGF-A expression only occurred after oxidative modification of low density lipoproteins, a process known to be important in atherogenesis. The non-atherogenic high density lipoproteins did not modulate the PDGF-A mRNA levels in smooth muscle cells. Consequently, oxidized low density lipoproteins may participate in atherosclerotic lesion formation as a result of autocrine stimulation of PDGF-A.
Zwijsen
R M
RM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Japenga
S C
SC
Heijen
A M
AM
van den Bos
R C
RC
Koeman
J H
JH
D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D046911:Macromolecular Substances; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D002084:Butylated Hydroxytoluene