Global Reach 2018: Dysfunctional Extracellular Microvesicles in Andean Highlander Males with Excessive Erythrocytosis.

High altitude-related excessive erythrocytosis (EE) is associated with increased cardiovascular risk. The experimental aim of this study was to determine the effects of microvesicles isolated from Andean highlanders with EE on endothelial cell inflammation, oxidative stress, apoptosis and nitric oxide (NO) production.Twenty-six male residents of Cerro de Pasco, Peru (4,340 m) were studied: 12 highlanders without EE (age: 40±4 yr; BMI: 26.4±1.7; Hb: 17.4±0.5 g/dL, SpO2: 86.9±1.0%) and 14 highlanders with EE (43±4 yr; 26.2±0.9; 24.4±0.4 g/dL;79.7±1.6%). Microvesicles were isolated, enumerated and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with microvesicles from highlanders without and with EE. Microvesicles from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8±2.7 vs 77.1±1.9 pg/mL) and IL-8 (62.0±2.7 vs 53.3±2.2 pg/mL) compared with microvesicles from healthy highlanders. Although intracellular expression of total NF-kB p65 (65.3+6.0 vs 74.9+7.8.9 AU) was not significantly affected, microvesicles from highlanders with EE resulted in ~25% higher (P<0.05) expression of p-NF-kB p65 (173.6+14.3 vs 132.8+12.2 AU) in cells treated with microvesicles from highlanders with EE. Cell reactive oxygen species production was significantly higher (76.4.7±5.4 vs 56.7±1.7 % of control) and endothelial nitric oxide synthase (p-eNOS) activation (231.3±15.5 vs 286.6±23.0 AU) and NO production (8.3±0.6 vs 10.7±0.7 μM/L) significantly lower in cells treated with microvesicles from highlanders with vs without EE. Cell apoptotic susceptibility was not significantly affected by EE-related microvesicles.Circulating microvesicles from Andean highlanders with EE increase endothelial cell inflammation and oxidative stress and reduced NO production.