Increased platelet aggregation in diabetic patients with microangiopathy despite good glycemic control

Citation
K. Kajita et al., Increased platelet aggregation in diabetic patients with microangiopathy despite good glycemic control, PLATELETS, 12(6), 2001, pp. 343-351
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
PLATELETS
ISSN journal
0953-7104 → ACNP
Volume
12
Issue
6
Year of publication
2001
Pages
343 - 351
Database
ISI
SICI code
0953-7104(200109)12:6<343:IPAIDP>2.0.ZU;2-P
Abstract
The pathogenesis of diabetic micro- and macroangiopathy cannot be fully exp lained by hyperglycemia alone. To clarify diabetic complications mediated b y increased platelet activity, we have studied platelet aggregation and its second messenger molecules such as protein kinase C (PKC), RhoA, and phosp hatidylinositol 3-kinase (PI3-kinase), in six diabetic patients with diabet ic retinopathy and other diabetic complications in spite of good glycemic c ontrol. Their HbA(1c) levels throughout the observation period had been les s than 6% with diet treatment alone, despite which diabetic retinopathy dev eloped to the pre-proliferative stage during 2-8 years observation. Low-dos e thrombin (<0.5 U/ml)-stimulated platelet aggregation in the diabetic pati ents was enormously elevated compared with healthy control subjects. PKC, R hoA and PI3-kinase activities in the cytosol- and membrane-associated fract ions were examined in the platelets from the two patients (Cases 2 and 4). Platelet membrane-associated RhoA and PI3-kinase activity in Case 2 were in creased before the stimulation. Platelet RhoA and PI3-kinase activities in Case 4 were increased after the stimulation with low-dose thrombin (0.01 U/ ml). Membrane-associated immunoreactive PKC<alpha>, but not PKC beta in Cas es 2 and 4 was elevated. Although platelet hyperactivity in these four pati ents was observed, PKC and RhoA in mononuclear leukocytes from these patien ts were not different from healthy subjects. Membrane-associated PKC alpha and RhoA immunoreactivities also increased in the other three cases. These results suggest that hyperreactivity of PKC alpha may lead to increased Rho A and PI3- kinase activities and platelet hyperfunction in diabetic patient s with good glycemic control, and that raised platelet PKC alpha may be imp licated in the pathogenesis of diabetic complications.