Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Abstract

Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O 2 ؊ was linked to both reduced expression of p47 phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction. (Am J Pathol

Blood-Based Biomarkers for Metabolic Syndrome

“…However, trends are pointing towards a relationship between the quantities of blood-based EVs and MetS. When plasma specimens from individuals ( Table 2, row A) with MetS were compared to those from healthy controls, a significant (P<0.001) increase in quantities of EVs (as determined by flow cytometry following labelling of EVs with antibodies against surface antigens) was observed with MetS [16]. A follow-up study ( Table 2, row B) confirmed these results and found circulating quantities of plasma EVs (as determined by flow cytometry) to be significantly (P<0.05) higher in MetS compared with healthy individuals [17].…”

Microparticles as Biomarkers of Vascular Dysfunction in Metabolic Syndrome and its Individual Components

“…In addition, when stimulated in vitro, platelets are the cells that produce microparticles most rapidly. However, although circulating levels of platelet-derived microparticles are often increased under pathological conditions, changes in other subpopulations of microparticles, such as non-platelet-derived microparticles or more specifically endothelial-derived microparticles, seems to have more significant pathological relevance [15,19,14]. In this respect, microparticles originating from a specific cell may be a signature of injury of that type of cells.…”

“…However, other microparticle subpopulations such as those from endothelial cells, red cells or leukocytes can also be increased as described in the metabolic syndrome [14], acute coronary syndrome [15], severe hypertension [16] and type 2 diabetes [17]. All these pathologies are associated with endothelial dysfunction and microcirculation disturbances suggesting that microparticles may, at least in part, play a key role in the pathogenesis of these diseases.…”

Childhood obesity–related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements

“…To our knowledge, the effect of a diet plus exercise treatment on numbers of circulating EMP in obese children had not been described before. Interestingly, microparticles, including EMP, may either be viewed as beneficial or detrimental (73), and further information on EMP in obese children would therefore be of interest.…”