0274 : Exosomes from metabolic syndrome patients induce endothelial dysfunction through mitochondrial-generated oxidative stress

Abstract

Metabolic syndrome (MetS) is characterized by a cluster of interrelated risk factors hyperglycemia, dyslipidemia, hypertension and obesity leading to an increased risk of cardiovascular events. Exosomes are nanoscaled vesicles (30 100 nm) released by cells, that bear proteins and nucleic acids. It has been demonstrated that circulating exosome rate is positively correlated with (i) an increase of inflammation, (ii) a decrease of HDL cholesterol and (iii) prevalence of MetS. However, it is unknown whether exosomes from MetS patients can act as biological vectors through their interaction with target cells.We hypothesized that exosomes may be implicated in MetS associated endothelial dysfunction. Circulating exosomes from healthy subjects and MetS patients have been isolated from plasma and, then, characterized. As expected, isolated exosomes have an average size of 63±15 nm and are enriched in exosomal specific proteins, tetraspanins such as CD81, CD9, CD63 and endolysosomal protein TSG101. Moreover, the majority of plasmatic exosomes are from leukocyte and platelet origins in both healthy subjects and MetS patients. MetS patients display increased levels of exosomes compared to healthy subjects. We demonstrated that treatment of human endothelial aortic cells with exosomes from MetS patients induce endothelial dysfunction associated with decreased nitric oxide and increased reactive oxygen species (ROS) production. The increase on fluorescence associated to Mitosox suggests an enhanced production of mitochondrial ROS following 4 hours of MetS exosome treatment. These data provide evidence that circulating exosomes from MetS patients induce endothelial dysfunction via both increased oxidative stress and reduced nitric oxide production. Altogether, we show exosomes as novel players implicated in endothelial dysfunction associated with MetS and consequently potential targets to prevent and treat vascular consequences of this syndrome. The author hereby declares no conflict of interest