SO020
ELEVATED SERUM PLATELET MICROPARTICLES CONTRIBUTE TO AORTA ENDOTHELIAL INJURY: A POTENTIAL NEW MECHANISM FOR ATHEROSCLEROSIS IN DIABETES

Introduction and Aims: An early complication in diabetes is the development of endothelial dysfunction, characterized by altered endothelial cell function, impaired nitric oxide (NO) bioavailability and accelerated thrombosis. Platelet microparticles (PMPs) are arousing interest due to their pro-inflammatory effects. This study aimed to investigate the role of PMPs in aortic endothelial injury in diabetes.

Methods: Eight-week old male Sprague-Dawley rats were divided into three groups: nondiabetic rats (control), streptozotocin-induced diabetic rats (DM), and diabetic rats treated with Aspirin (DM+ Aspirin). The determination of PMPs was used by flow cytometry and confocal microscopy. The inflammatory cytokines released from PMPs was checked by protein microarray, immunohistochemical staining, or Western blot. The aortic endothelial injury was evaluated through determination of NO concentration, measuring the expression of endothelial nitric oxide synthase (eNOS), the change of glycocalyx and aortic endothelial permeability by electron microscopy, immunofluorescent staining and Western blot.

Results: Compared to the control, the serum level of PMPs increased significantly in DM rats, which was inhibited by Aspirin. Aspirin treatment decreased the production of inflammatory cytokines from serum PMPs and aorta. Using confocal microscopy, the enhanced interaction between PMPs and aortic endothelium was observed in DM rats, which was inhibited by Aspirin. Interestingly, the elevated PMPs and production of inflammatory cytokines from PMPs were correlated with the aortic endothelial injury by decreasing the NO excretion, the expression of eNOS, glycocalyx thickness and increasing endothelial permeability in DM rats. Decreased serum PMPs and production of inflammatory cytokines by Aspirin ameliorated the aortic endothelial injury compared to the DM group.

Conclusions: Elevated serum PMPs contribute to aorta endothelial injury through the release of inflammatory cytokines from PMPs, which accelerate the progression of atherosclerosis in diabetes.