Increased aggregation of human platelets produced by advanced glycation end products in vitro.
Advanced glyco-oxidation end products (AGEs) generate oxygen free radicals that potentiate the development of atherosclerosis. Thus, AGEs may potentiate the aggregation of human platelets through oxidative stress. AGE-bovine serum albumin (BSA) and AGE-poly-L-lysine were evaluated for aggregation of human platelets. Superoxide in platelet-rich plasma (PRP) was measured using lucigenin-derived chemiluminescence. The platelet aggregation induced by ADP or U46619 was potentiated by preincubation with AGE-BSA, by 40% and by 59%, P < .05, respectively, vs BSA. Aggregation was increased by AGEs in a dose-dependent manner. The production of superoxide was significantly greater in PRP incubated with AGE-BSA vs BSA. The other Maillard reaction products, such as Amadori-, pentosidine-, and carboxymethyl lysine (CML)-BSA had no effect. Superoxide dismutase or indomethacin abolished the enhancing effect of AGEs on the platelet aggregation. AGEs potentiate platelet aggregation possibly with superoxide anions and prostanoids. AGE-induced potentiation of platelet aggregation may be involved in the development of atherosclerosis.
Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
M
M
Hangaishi
J
J
Taguchi
T
T
Miyata
Y
Y
Ikari
M
M
Togo
Y
Y
Hashimoto
T
T
Watanabe
S
S
Kimura
K
K
Kurokawa
M
M
Ohno
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis; D001161:Arteriosclerosis / Q000503:physiopathology; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011107:Polylysine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D017127:Glycation End Products, Advanced; D011453:Prostaglandins; D017382:Reactive Oxygen Species; C081628:advanced glycation end products-bovine serum albumin; D013481:Superoxides; D011107:Polylysine; D012710:Serum Albumin, Bovine; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; C062187:pentosidine; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D008239:Lysine; D007213:Indomethacin