Modification of prostaglandin synthesis in washed human platelets and cultured bovine aortic endothelial cells by glycosylated low density lipoprotein.
Glycosylation of low-density lipoprotein (LDL) is known to be increased in diabetic patients. Recent studies have demonstrated that glycosylated (glc-) LDL contributes to the acceleration of atherosclerosis in diabetes. In the present study, we evaluated the effect of glc-LDL prepared in vitro on platelet aggregation and thromboxane B2 (TxB2) production in washed human platelets and on 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) production by cultured bovine aortic endothelial cells. After preincubation of washed platelets with glc-LDL or control LDL, thrombin-induced platelet aggregation and TxB2 production were measured. Control LDL enhanced the platelet aggregation rate and TxB2 production in a time- and dose-dependent manner. Glc-LDL showed significantly greater enhancement of those platelet functions than control LDL. On the other hand, while 6-keto-PGF1 alpha production was stimulated by control LDL in a time- and dose-dependent manner, glc-LDL significantly reduced the stimulatory effect of control LDL on 6-keto-PGF1 alpha production. These results suggest that modification of prostaglandin synthesis in platelets and endothelial cells by glycosylated LDL may lead to platelet hyperaggregation and thrombus formation in diabetes.
Ishii
H
H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Umeda
F
F
Kunisaki
M
M
Yamauchi
T
T
Nawata
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood; D000093844:Glycated Proteins
D015121:6-Ketoprostaglandin F1 alpha; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D011453:Prostaglandins; D013929:Thromboxane B2; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins