Platelet Sarcoplasmic Endoplasmic Reticulum Ca 2+ -ATPase and μ-Calpain Activity Are Altered in Type 2 Diabetes Mellitus and Restored by Rosiglitazone

• DOI: 10.1161/circulationaha.107.719807
• Publication Date: 2007-12-11T01:46:43Z
• Authors: Voahanginirina Ra...; Frank Pistrosch; Birgit Bölck; Robert H.G. Schwi...; Madhulika Dixit; Klaus Badenhoop; Richard A. Cohen; Rudi Busse; Ingrid Fleming
• Keywords: Rosiglitazone

Platelets from patients with type 2 diabetes mellitus display hyperaggregability and increased thrombogenic potential.In platelets mellitus, we found enhanced tyrosine nitration inactivation of the sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA-2), elevated platelet [Ca2+]i, activation mu-calpain. The SERCA-2 mu-calpain in vitro healthy volunteers could be evoked by peroxynitrite. Platelet endothelial cell adhesion molecule-1 was identified as a substrate; its degradation stimulated peroxynitrite prevented calpain inhibitors. Calpain also linked to hyperresponsiveness thrombin loss sensitivity nitric oxide synthase (hemoglobin A1c >6.6%) contained little or no intact molecule-1, whereas products were detectable. peroxisome proliferator-activated receptor-gamma agonist rosiglitazone expression megakaryocytes, treating for 12 weeks activity, decreased nitration, normalized [Ca2+]i. Rosiglitazone reduced levels, partially restored inhibition.These data identify megakaryocytes/platelets additional cellular targets agonists highlight potential benefits therapy cardiovascular diseases.