Endothelial dysfunction, e.g. in atherosclerosis, is accompanied by the release of microparticles (MP). In this study, we sought to investigate the effect of moderate hypoxia on circulatory levels of microparticles, biomarkers of cardiovascular function and inflammation and on echocardiographic parameters in healthy volunteers staying at an altitude of 2978 m. Methods: Eighteen healthy volunteers were subjected to moderate hypoxia by staying at a mountain lodge in Diavolezza, Switzerland (2978

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... above sea level). Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for four novel cardiovascular biomarkers, namely suppression of tumorigenicity (ST2, indicating haemodynamic stress), growth-differentiation factor-15 (GDF-15, indicating remodeling), urokinase plasminogen activator receptor (uPAR, indicating inflammation) and heart-type fatty acid binding protein 3 (H-FABP, indicating sub-clinical ischaemia). Moreover, the effect of dual endothelinreceptor blockade (by macitentan) on MP, sST2, H-FABP, suPAR, GDF-15 and echocardiographic parameters was investigated at moderate altitude and during physical exercise. Results: During the experiment, oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. For example, CD31+/CD42-MP concentration at baseline was 5.09% (±1.26% SEM) at the start of the experiment. After acclimatization at 2978 m above mean sea level, MP levels evidenced a significant decline to 1.19% (±0.14% SEM). After returning to 143 m a significant rise to 2.88% (±0.43% SEM) was recorded again. These results were corroborated by a similar response in sST2, H-FABP and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on EMP, sST2, H-FABP, suPAR and GDF-15 levels, though it led to a significant amelioration of echocardiographic parameters of right heart function. Conclusions: These experimental results show that moderate hypoxia due to altitude exposition led to a reduction in parameters of endothelial dysfunction as shown by a decrease in endothelial and platelet MP, sST2 and suPAR levels. A slight increase in pulmonary pressure in moderate altitude was decreased by dual endothelin receptor blockade.