Elevated levels of circulating microvesicles in coronary artery disease patients with type 2 diabetes and albuminuria: Effects of exercise training

Abstract

Objective:Circulating microvesicles, released from activated/apoptotic cells, are involved in vascular complications and may be looked upon as biomarkers. Albuminuria is characteristic of disease progression in type 2 diabetes mellitus. We aimed to investigate quantitative and qualitative differences of circulating microvesicles in type 2 diabetes mellitus with and without albuminuria and whether 12-month exercise training influenced expression of circulating microvesicles.Methods:Coronary artery disease patients with type 2 diabetes mellitus (n = 75), of which 25 had albuminuria, were included. Annexin V+(AV+) circulating microvesicles were analysed by flow cytometry in citrated plasma. The exercise volume was 150 min per week.Results:In albuminuria patients, circulating microvesicles from endothelial-(CD146+/CD62E+/AV+) and endothelial-progenitor-(CD309+/CD34+/AV+) cells were significantly higher compared to those without ( p ⩽ 0.01, both). Receiver operating characteristic curve analysis of the endothelial circulating microvesicles shows an area under the curve of 0.704 (95% confidence interval: 0.57–0.84; p = 0.004). Albuminuria patients had more circulating microvesicles derived from activated leukocytes and monocytes and monocytes carrying tissue factor (CD11b+/AV+, CD11b+/CD14+/AV+, CD142+/CD14+/AV+, respectively, p ⩽ 0.05, all) and higher number of circulating microvesicles from activated platelets (CD62P+/AV+). Within exercising patients, circulating microvesicles from progenitor cells increased ( p = 0.023), however, not significantly different from controls.Conclusion:Coronary artery disease patients with type 2 diabetes mellitus and albuminuria had elevated number of circulating microvesicles from activated blood and vascular cells, rendering them as potential predictors of disease severity. The circulating microvesicles were limitedly affected by long-term exercise training in our population.

Platelets at the Crossroads of Pro-Inflammatory and Resolution Pathways during Inflammation

“…Elevated PMV levels were associated with glycaemic profiles and amplified thrombotic tendencies [ 65 ]. Similar observations were reported by Bratseth and colleagues, highlighting elevated PMV levels in coronary artery disease patients with type 2 diabetes and albuminuria as potential predictors of disease severity [ 66 ]. In a project investigating the influence of PMVs in early diabetic nephropathy Zhang et al revealed that PMVs induce the production of reactive oxygen species (ROS), decrease nitric oxide levels and promote barrier permeability in glomerular endothelial cells.…”

Frail older adults show a distinct plasma microvesicle profile suggesting a prothrombotic and proinflammatory phenotype

“…Also, some cMVs expose phosphatidylserine (PS) at the outer leaflet during their biogenesis, conferring procoagulant activity, thus promoting the development and progression of atherothrombosis (Suades, Padro, Vilahur, & Badimon, 2012). High levels of cMVs have been related to the severity of acute myocardial infarction, both in patients with diabetes or coronary heart disease (Bratseth et al, 2019;Suades et al, 2012). Due to their molecular load, cMVs seem to contribute both to the onset and progression of vascular disease and also to participate in the occurrence of clinical events (Ridger et al, 2017).…”

Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome

“…T2DM patients obtained benefits of physical training too. T2DM patients with coronary artery disease, albuminuria, and microalbuminuria had higher levels of circulating endothelial related EVs, monocyte-derived EVs, platelet-derived Evs, and EVs from endothelial progenitor cells (EPCs) [ 235 ]. Increased circulating EVs from endothelial cells indicate vascular injury progression, atherosclerosis, and nephropathy [ 124 , 236 , 237 , 238 ].…”