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Circulating microparticles from diabetic rats impair endothelial function and regulate endothelial protein expression
K Ishida1, K Taguchi1, M Hida1
1Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Aim:
Diabetes mellitus increases the risk of cardiovascular disease, which is accompanied by functional and structural changes in the vascular system. Microparticles (MPs) 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 MPs derived from streptozotocin (STZ)-induced diabetic rats in endothelial function.
Methods:
Male Wistar rats were injected with STZ to induce diabetes, and MPs isolated from control or STZ-induced diabetic rats were characterized by dot blotting (assessed by CD62P detections), flow cytometry (assessed by annexin V detections) and ELISA. Carotid arteries from rats were incubated with MPs, and expressions of enzymes and endothelium-dependent relaxation were analysed.
Results:
The circulating levels of MPs, 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 MPs isolated from STZ rats, ACh-induced endothelium-dependent relaxation was impaired, but MPs isolated from control rats had no such effect. Furthermore, the effect of MPs was mediated by a decrease in expression of endothelial nitric oxide synthase (eNOS) and the overexpression of caveolin-1.
Conclusion:
Circulating MPs isolated from STZ-induced diabetic rats induce endothelial dysfunction in carotid arteries and regulate protein expressions of eNOS and caveolin-1. These data advance our understanding of the deleterious effects of circulating MPs observed in disorders with diabetic complications.
Insights
Microparticles (MPs) from diabetic rats impair blood vessel function by altering endothelial nitric oxide synthase (eNOS) and caveolin-1 levels. These findings highlight MPs' role in diabetic vascular complications.
Area of Science:
- Vascular Biology
- Endocrinology
- Cardiovascular Disease
Background:
- Diabetes mellitus is a major risk factor for cardiovascular disease, associated with vascular dysfunction.
- Microparticles (MPs) are implicated in endothelial dysfunction, but their specific roles and mechanisms in diabetes are not fully understood.
Purpose of the Study:
- To investigate the impact of MPs from streptozotocin (STZ)-induced diabetic rats on endothelial function.
- To elucidate the molecular mechanisms by which these MPs affect vascular health.
Main Methods:
- Diabetes was induced in Wistar rats using STZ.
- MPs were isolated from control and diabetic rats and characterized.
- Carotid arteries were incubated with MPs to assess endothelium-dependent relaxation and protein expression (eNOS, caveolin-1).
Main Results:
- Diabetic rats exhibited higher circulating MP levels, particularly platelet-derived MPs.
- MPs from diabetic rats impaired acetylcholine-induced endothelium-dependent relaxation in control carotid arteries.
- This impairment was linked to reduced endothelial nitric oxide synthase (eNOS) and increased caveolin-1 expression.
Conclusions:
- Circulating MPs from diabetic rats induce endothelial dysfunction.
- These MPs modulate eNOS and caveolin-1 protein expression, contributing to vascular complications in diabetes.
