Increased Aggregated Circulating Microparticles in STZ‐induced Diabetic Rats Propagate Inflammation

Abstract

Increased circulating microparticles (MPs) have been found to be associated with many cardiovascular diseases. However, the detailed profile of increased MPs in diabetic animals and their roles in the development of vascular complications are yet to be identified. The objective of this study is to characterize the profiles of plasma MPs in normal and STZ-induced diabetic rats, and investigate how the increased MPs affect microvessel functions. Flow cytometry was used to quantify plasma MPs, and identify MPs cell origins using antibodies directly against cell specific antigens. Results showed that plasma MPs increased remarkably from 4.8 ± 0.7 in normal to 727.2 ± 312.4 (×104/µl) in diabetic rats, and the majority of the increased MPs existed as aggregated units that expressed multiple parental cell antigens. About 49.6% of the MPs carried triple antigens: leukocyte (CD45), platelet (CD61), and endothelial cell (EC, CD144); and 36.7% MPs carried CD45 and CD61. When diabetic plasma was perfused into a normal venule, illustrated by annexin V staining and confocal imaging, a significant number of MPs adhered to the vessel wall. When blood flow was resumed in the diabetic plasma perfused vessels, the adhered MPs cause significantly increased leukocyte adhesion compared to normal plasma perfused vessels. These results suggest that most of the increased MPs in diabetic rats originated from leukocyte, platelet, and ECs and exist as aggregate form other than individuals. The increased circulating MPs are capable to interact with normal ECs, mediate leukocyte adhesion, and propagate the inflammation to normal vasculature. Supported by HL56237 and HL084338.