IDL can stimulate atherogenic gene expression in cultured human vascular endothelial cells

Previously, we have reported that the lipoprotein fraction containing inter mediate density lipoprotein (IDL) and low density lipoprotein (LDL) isolate d from diabetics stimulates an atherogenic cytokine in cultured endothelial cells. To study which lipoprotein fraction isolated from diabetics can mod ulate the gene expression in endothelial cells, we isolated IDL and LDL fra ctions from 14 type 2 diabetics and seven age- and BMI- adjusted non-diabet ics. We measured the effects of the lipoproteins on mRNA expression of athe rogenic molecules in cultured endothelial cells. We found that the IDL frac tion stimulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in endothelial cells as time- and dose-dependent fashions, while the LDL fr action was not effective. IDL isolated from diabetics also increased not on ly platelet-derived growth factor B-chain, but also intercellular adhesion molecule-1 mRNA contents. Furthermore, the HbA(1c) levels in diabetics were significantly correlated with their abilities of IDL to increase MCP-1 mRN A content in the cells and the increment coincided with the increase in MCP -I protein release into culture media. These results indicate that qualitat ive as well as quantitative changes in IDL fraction in diabetes are atherog enic through stimulating gene expression of atherogenic molecules in endoth elial cells. (C) 2000 Elsevier Science Ireland Ltd. All lights reserved.