Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

Centro de Investigaciones Biologicas Consejo Superior de Investigaciones Cientificas CSIC and Centro de Investigacion Biomedica en Red de Enfermedades Raras 28040 Madrid Spain

Department of Biological and Medical Sciences Faculty of Pharmacy in Hradec Kralove Charles University Prague Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

Jagiellonian Centre for Experimental Therapeutics Bobrzynskiego 14 30 348 Krakow Poland

Jagiellonian Centre for Experimental Therapeutics Bobrzynskiego 14 30 348 Krakow Poland; Department of Experimental Pharmacology Chair of Pharmacology Medical College Jagiellonian University Grzegorzecka 16 31 531 Krakow Poland

Renal and Cardiovascular Physiopathology Unit Department of Physiology and Pharmacology University of Salamanca 37007 Salamanca Spain

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