Activated platelet and oxidized LDL induce endothelial membrane vesiculation: clinical significance of endothelial cell-derived microparticles in patients with type 2 diabetes.
Endothelial cells, platelets, and oxidized LDL could play very important roles in the development of atherosclerosis in diabetes patients. The levels of plasma endothelial cell-derived microparticles (EDMP), platelet-derived microparticles (PDMP), platelet-P-selectin (plt-PS), soluble CD40 ligand (sCD40L), and anti-oxidized LDL antibody were measured and compared to develop a better understanding of their potential contribution to diabetic vascular complications. The concentrations of EDMP, PDMP, plt-PS, and sCD40L in diabetic patients were significantly higher than those in normal subjects. The number of EDMPs in patients with diabetes complicated by nephropathy was significantly higher than that in those without complications. Levels of anti-oxidized LDL antibody were also higher in type 2 diabetic patients than in control subjects. In addition, anti-oxidized LDL antibody levels correlated with EDMP, PDMP, plt-PS, and sCD40L levels in nephropathy patients. In the nephropathy group treated with sarpogrelate hydrochrolide, a 5-HT(2A) receptor antagonist, EDMP, PDMP, plt-PS, and sCD40L levels were decreased significantly. Oxidized LDL increased expression of plt-PS, and also promoted shedding of PDMP. Furthermore, oxidized LDL promoted a dose-dependent release of 5-hydroxytriptamine. On the other hand, activated platelets and PDMP promoted endothelial cells and THP-1 (monocytic cell line) interaction, and membrane vesiculation occurred in the presence of oxidized LDL. These findings suggest that activated platelets and oxidized LDL induce EDMP generation, and that elevated EDMPs may be a sign of vascular complications in type 2 diabetic patients, particularly those who suffer from diabetes-associated nephropathy.
Nomura
Shosaku
S
First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan. shosaku-n@mbp.ocn.ne.jp
Shouzu
Akira
A
Omoto
Seitaro
S
Nishikawa
Mitsushige
M
Iwasaka
Toshiji
T
Fukuhara
Shirou
S
D001161:Arteriosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D023201:CD40 Ligand / Q000032:analysis; D002448:Cell Adhesion; D002462:Cell Membrane / Q000648:ultrastructure; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D019007:P-Selectin / Q000032:analysis; D010316:Particle Size; D015539:Platelet Activation; D012701:Serotonin / Q000378:metabolism
D001323:Autoantibodies; D008077:Lipoproteins, LDL; D019007:P-Selectin; C099252:oxidized low density lipoprotein; D023201:CD40 Ligand; D012701:Serotonin