Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt-Endothelial NO Synthase Signaling PathwayReportar como inadecuado




Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt-Endothelial NO Synthase Signaling Pathway - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. The purpose of this study was to characterize circulating platelets in diabetes and clarify their effects on endothelial function. Male Wistar rats were injected with streptozotocin STZ to induce diabetes. Each experiment was performed by incubating carotid arterial rings with platelets 1.65×107 cells-mL; 30 min isolated from STZ or control rats. Thereafter, the vascular function was characterized in isolated carotid arterial rings in organ bath chambers, and each expression and activation of enzymes involved in nitric oxide and oxidative stress levels were analyzed. Endothelium-dependent relaxation induced by acetylcholine was significantly attenuated in carotid arteries treated with platelets isolated from STZ rats. Similarly, treatment with platelets isolated from STZ rats significantly reduced ACh-induced Akt-endothelial NO synthase signaling-NO production and enhanced TXB2 metabolite of TXA2, while CD61 platelet marker and CD62P activated platelet marker were increased in carotid arteries treated with platelets isolated from STZ rats. Furthermore, the platelets isolated from STZ rats decreased total eNOS protein and eNOS dimerization, and increased oxidative stress. These data provide direct evidence that circulating platelets isolated from diabetic rats cause dysfunction of the endothelium by decreasing NO production via Akt-endothelial NO synthase signaling pathway and increasing TXA2. Moreover, activated platelets disrupt the carotid artery by increasing oxidative stress.



Autor: Keiko Ishida, Kumiko Taguchi, Takayuki Matsumoto, Tsuneo Kobayashi

Fuente: http://plos.srce.hr/



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