Oxidized lipoproteins found in patients with NIDDM stimulate radical-induced monocyte chemoattractant protein-1 mRNA expression in cultured human endothelial cells.
Although oxidized low density lipoprotein (LDL) exists in plasma from diabetic patients, there are few studies on its biological activity. Thus, we investigated the biological potency of LDL plus intermediate density lipoprotein fraction isolated from 12 non-diabetic and 24 non-insulin-dependent diabetic subjects of similar age and body mass index, in order to induce monocyte chemoattractant protein-1 (MCP-1) mRNA expression in cultured human endothelial cells. MCP-1 mRNA content in the cells exposed to the lipoproteins isolated from the diabetic patients was significantly higher than that from the control subjects (p < 0.001). The increment of MCP-1 mRNA content was positively correlated with not only HbA1c (r = 0.58, p < 0.0001) but also lysophosphatidylcholine (LPC) content in the lipoprotein (r = 0.46, p < 0.005) and was negatively correlated with diene formation lag time as a marker of oxidizability of the lipoprotein (r = -0.33, p < 0.05). Treatments of the cells with either 50 mumol/l probucol, 50 mumol/l alpha-tocopherol, or 0.1 mmol/l deferoxamine suppressed the increase in MCP-1 mRNA content induced by diabetic lipoproteins, respectively. Furthermore, the diabetic lipoproteins activated nuclear transcription factor NF-kappa B in the cells, which was inhibited by pre-treatment of cells with 50 mumol/l probucol. These data indicate that oxidatively modified lipoproteins found in diabetic plasma stimulate MCP-1 gene expression in endothelial cells. The LPC content which reflects oxidative modification of lipoprotein is at least a possible marker of biological activity to increase an atherogenic cytokine in endothelial cells.
Takahara
N
N
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kashiwagi
A
A
Nishio
Y
Y
Harada
N
N
Kojima
H
H
Maegawa
H
H
Hidaka
H
H
Kikkawa
R
R
D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003676:Deferoxamine / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011341:Probucol / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D012044:Regression Analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D018932:Chemokine CCL2; D008074:Lipoproteins; D012333:RNA, Messenger; D014810:Vitamin E; D003676:Deferoxamine; D011341:Probucol