Acute effects of moderate altitude on biomarkers of cardiovascular inflammation and endothelial function and their differential modulation by dual endothelin receptor blockade

Article type: Research Article

Authors: Lichtenauer, Michael^a | Goebel, Bjoern^b | Paar, Vera^a | Wernly, Bernhard^a | Gecks, Thomas^b | Rohm, Ilonka^b | Förster, Martin^b | Betge, Stefan^b | Figulla, Hans R.^b | Hoppe, Uta C.^a | Kelm, Malte^c | Franz, Marcus^b | Jung, Christian^{c; *}

Affiliations: [a] Department of Cardiology, Clinic of Internal Medicine II, Paracelsus Medical University of Salzburg, Austria | [b] Department of Internal Medicine I, Jena University Hospital, Friedrich Schiller University Jena, Germany | [c] Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Germany

Correspondence: [*] Corresponding author: Christian Jung, MD, PhD, University Hospital Düsseldorf, Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine, 40225 Düsseldorf, Germany. Tel.: +49 211 81 18800; Fax: +49 211 81 18812; E-mail: Christian.Jung@med.uni-duesseldorf.de.

Abstract: BACKGROUND:Endothelial dysfunction is accompanied by the release of microparticles (MP). OBJECTIVE: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 2978 m above sea level for three days. Blood samples were evaluated for MP using flow cytometry. ELISA analysis was performed for sST2, H-FABP, suPAR and GDF-15. Moreover, the effect of dual endothelin-receptor blockade was investigated. RESULTS:Oxygen saturation decreased to 93%. A significant decrease of endothelial and platelet MP levels was found. These results were corroborated by a similar response in sST2 and suPAR plasma concentration. Endothelin-receptor blockade by macitentan only had a marginal influence on MP, 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 at moderate altitude was decreased by dual endothelin receptor blockade.

Keywords: Endothelial dysfunction, microparticles, biomarkers, sST2, H-FABP, suPAR, GDF-15, endothelin, hypoxia, moderate altitude

DOI: 10.3233/CH-170273

Journal: Clinical Hemorheology and Microcirculation, vol. 67, no. 1, pp. 101-113, 2017