Effect of glucose concentration on foam cell formation in THP-1 cells.
We investigated whether a high glucose condition could affect cholesterol ester (CE) synthesis and accumulation of cholesterol in arterial wall cells by using the human monocytic cell line THP-1. After 24-hour PMA treatment, cells were grown in control (200 mg/dl of glucose) or high glucose concentration (400, 600, 800, or 1,600 mg/dl) medium for 6 days. CE synthesis was then investigated in cells incubated with 50 microg/ml of native, glycated, acetylated, or oxidized LDL. Cells grown in 400 mg/dl of glucose showed a significant increase of CE synthesis regardless of whether they were incubated with native, glycated or oxidized LDL, compared with cells grown in 200 mg/dl of glucose. In parallel with the studies of CE synthesis, the intracellular accumulation of CE also increased in cells grown in 400 mg/dl of glucose when incubated with oxidized LDL (50 microg/ml), compared with that in cells grown in 200 mg/dl of glucose. The amount of oxidized LDL associated with cells grown in 400 mg/dl of glucose was markedly higher than that in cells grown in 200 mg/dl of glucose. This suggests that there is an optimal glucose concentration (400 mg/dl) which increases the number of some scavenger receptors (receptors for oxidized LDL) expressed on cells, and might increase and stimulate CE synthesis, resulting in intracellular accumulation of CE in macrophage. A high blood glucose concentration could change the metabolism of arterial wall cells and play an important role in the pathogenesis of vascular complications of diabetes mellitus.
Naito
T
T
Department of Internal Medicine, Saka General Hospital, Miyagi, Japan.
Oikawa
S
S
Kotake
H
H
Hayasaka
K
K
Toyota
T
T
D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D019301:Oleic Acid; D002784:Cholesterol; D005947:Glucose