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.