title: 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 Diet.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Jezkova
authors.forename: Jana
authors.initials: J
authors.lastname: Rathouska
authors.forename: Ivana
authors.initials: I
authors.lastname: Nemeckova
authors.forename: Petra
authors.initials: P
authors.lastname: Fikrova
authors.forename: Eva
authors.initials: E
authors.lastname: Dolezelova
authors.forename: Michala
authors.initials: M
authors.lastname: Varejckova
authors.forename: Barbora
authors.initials: B
authors.lastname: Vitverova
authors.forename: Kristyna
authors.initials: K
authors.lastname: Tysonova
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Serwadczak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Buczek
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
authors.forename: Petr
authors.initials: P
authors.lastname: Nachtigal
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000071063:Endoglin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D018836:Inflammation Mediators; D014665:Vasodilator Agents; D009569:Nitric Oxide