Abstract
Diabetes is commonly associated with microvascular dysfunction. Our previous study found that microvessels of diabetic rats had increased basal permeability and enhanced permeability responses to inflammatory mediators. We also found that diabetic rats had increased circulating microparticles (MPs). MPs are small vesicles released by activated or apoptotic cells and carry multiple antigens from activated cells. We hypothesized that MPs serve as vectors to actively disseminate inflammation to the whole vascular system. We used flow cytometry to quantify the numbers of MPs and their cell origins. We tested differences between MPs generated by diabetic rats and MPs from normal rats by directly perfusing them into intact microvessels. The effects of MPs on microvessel walls were examined by perfusing matched numbers of isolated Annexin V positive MPs into normal venules for 30 min. After 10 min resumed blood flow in MP perfused vessel, we found significantly higher number of adherent leukocytes in diabetic MP perfused vessels than in normal MP perfused vessels. Diabetic and normal MP‐ mediated leukocyte adhesion were 17 ± 2.9 and 5.7 ± 0.5 leukocytes per 100 μm of vessel length, respectively. Flow cytometry analysis showed that diabetic MPs had an average 7‐fold increase in phosphatidylserine exposure per MP and a 12‐fold increase in platelet‐leukocyte MP aggregates from those in normal plasma MPs. Our results suggest that the population differences and the larger surface area of PS exposed diabetic MPs may contribute to the greater leukocyte adhesion induced by diabetic MPs. These results support our hypothesis that increased MPs in diabetic rats are more than simply biomarkers of the disease but that they are able to directly mediate leukocyte adhesion and actively disseminate inflammation to remote regions.Supported by: 1F32HL114376, P20GM103434, HL56237, HL084338
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