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Circulating microparticles from diabetic rats impair endothelial function and regulate endothelial protein expression
Author(s) -
Ishida K.,
Taguchi K.,
Hida M.,
Watanabe S.,
Kawano K.,
Matsumoto T.,
Hattori Y.,
Kobayashi T.
Publication year - 2016
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12561
Subject(s) - enos , medicine , endothelial dysfunction , endocrinology , endothelium , diabetes mellitus , streptozotocin , nitric oxide , vasodilation , chemistry , nitric oxide synthase
Aim Diabetes mellitus increases the risk of cardiovascular disease, which is accompanied by functional and structural changes in the vascular system. Microparticles ( MP s) have been described as biological vectors of endothelial dysfunction in other pathologies. However, the molecular mechanisms underlying their formation and signalling are unclear. We investigated the role of MP s derived from streptozotocin ( STZ )‐induced diabetic rats in endothelial function. Methods Male Wistar rats were injected with STZ to induce diabetes, and MP s isolated from control or STZ ‐induced diabetic rats were characterized by dot blotting (assessed by CD 62P detections), flow cytometry (assessed by annexin V detections) and ELISA . Carotid arteries from rats were incubated with MP s, and expressions of enzymes and endothelium‐dependent relaxation were analysed. Results The circulating levels of MP s, particularly the levels of platelet‐derived microparticles, from diabetic rats were higher than those present in controls. Endothelium‐dependent relaxation induced by acetylcholine (ACh) was attenuated in carotid arteries from STZ ‐induced diabetic rats. Following the incubation of control carotid arteries with MP s isolated from STZ rats, ACh‐induced endothelium‐dependent relaxation was impaired, but MP s isolated from control rats had no such effect. Furthermore, the effect of MP s was mediated by a decrease in expression of endothelial nitric oxide synthase (e NOS ) and the overexpression of caveolin‐1. Conclusion Circulating MP s isolated from STZ ‐induced diabetic rats induce endothelial dysfunction in carotid arteries and regulate protein expressions of e NOS and caveolin‐1. These data advance our understanding of the deleterious effects of circulating MP s observed in disorders with diabetic complications.