High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat DietJezkova K.a · Rathouska J.a · Nemeckova I.a · Fikrova P.a · Dolezelova E.a · Varejckova M.a · Vitverova B.a · Tysonova K.a · Serwadczak A.e · Buczek E.e · Bernabeu C.b, c · Lopez-Novoa J.M.d · Chlopicki S.e, f · Nachtigal P.a
aDepartment of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic; bCenter for Biological Research, Spanish National Research Council (CSIC), and cBiomedical Research Networking Center on Rare Diseases (CIBERER), Madrid, and dRenal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain; eJagiellonian Centre for Experimental Therapeutics (JCET), and fDepartment of Experimental Pharmacology, Medical College, Jagiellonian University, Krakow, Poland
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Aims: A soluble form of endoglin (sEng) was proposed to participate in the induction of endothelial dysfunction in small blood vessels. Here, we tested the hypothesis that high levels of sEng combined with a high-fat diet induce endothelial dysfunction in an atherosclerosis-prone aorta. Methods and Results: Six-month-old female and male transgenic mice overexpressing human sEng (Sol-Eng+) with low (Sol-Eng+low) or high (Sol-Eng+high) levels of plasma sEng were fed a high-fat rodent diet containing 1.25% cholesterol and 40% fat for 3 months. The plasma cholesterol and mouse sEng levels did not differ in the Sol-Eng+high and Sol-Eng+low mice. The expression of proinflammatory (P-selectin, ICAM-1, pNFκB and COX-2) and oxidative-stress-related markers (HO-1, NOX-1 and NOX-2) in the aortas of Sol-Eng+high female mice was significantly higher than in Sol-Eng+low female mice. Endothelium-dependent vasodilatation induced by acetylcholine was preserved better in the Sol-Eng+ high female mice than in the Sol-Eng+low female mice. Conclusion: These results suggest that high concentrations of sEng in plasma in combination with a high-fat diet induce the simultaneous activation of proinflammatory, pro-oxidative and vasoprotective mechanisms in mice aorta and the balance of these biological processes determines whether the final endothelial phenotype is adaptive or maladaptive.
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