IDL can stimulate atherogenic gene expression in cultured human vascular endothelial cells.
Previously, we have reported that the lipoprotein fraction containing intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) isolated from diabetics stimulates an atherogenic cytokine in cultured endothelial cells. To study which lipoprotein fraction isolated from diabetics can modulate the gene expression in endothelial cells, we isolated IDL and LDL fractions from 14 type 2 diabetics and seven age- and BMI- adjusted non-diabetics. We measured the effects of the lipoproteins on mRNA expression of atherogenic molecules in cultured endothelial cells. We found that the IDL fraction stimulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in endothelial cells as time- and dose-dependent fashions, while the LDL fraction was not effective. IDL isolated from diabetics also increased not only 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 mRNA content in the cells and the increment coincided with the increase in MCP-1 protein release into culture media. These results indicate that qualitative as well as quantitative changes in IDL fraction in diabetes are atherogenic through stimulating gene expression of atherogenic molecules in endothelial cells.
Maeno
Y
Y
Third Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Kashiwagi
A
A
Nishio
Y
Y
Takahara
N
N
Kikkawa
R
R
D001161:Arteriosclerosis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology*; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012333:RNA, Messenger; D012016:Reference Values; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood; D014471:Umbilical Veins
D018932:Chemokine CCL2; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol