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

Autor: Kristyna Tysonova, Jana Rathouska, Elzbieta Buczek, Michala Varejckova, Petr Nachtigal, Stefan Chlopicki, Carmelo Bernabeu, Barbora Vitverova, José M. López-Novoa, Petra Fikrova, Agnieszka Serwadczak, Eva Dolezelova, Ivana Nemeckova, K. Jezkova
Přispěvatelé: Czech Science Foundation, Charles University (Czech Republic), European Commission, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Instituto de Salud Carlos III, Jezkova, Katerina [0000-0001-5497-2313], Rathouska, Jana [0000-0001-6363-9715], Nemeckova, Ivana [0000-0002-9795-8471], Fikrova, Petra [0003-0484-6049], Dolezelova, Eva [0000-0002-1397-6016], Varejckova, Michala [0000-0002-5370-3194], Vitverova, Barbora [0000-0002-4446-2712], Buczek, Elzbieta [0000-0003-4955-3872], Bernabéu, Carmelo [0000-0002-1563-6162], López-Novoa, José M. [0000-0002-6211-7269], Chlopicki, Stefan [http://orcid.org/0000-0002-2878-3858, Nachtigal, Petr [0000-0001-9568-7295], Jezkova, Katerina, Rathouska, Jana, Nemeckova, Ivana, Fikrova, Petra, Dolezelova, Eva, Varejckova, Michala, Vitverova, Barbora, Buczek, Elzbieta, Bernabéu, Carmelo, López-Novoa, José M., Chlopicki, Stefan, Nachtigal, Petr
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Soluble endoglin
Physiology
Vasodilator Agents
Vasodilation
030204 cardiovascular system & hematology
medicine.disease_cause
Mice
0302 clinical medicine
hemic and lymphatic diseases
Endothelial dysfunction
Aorta
Chemistry
Endoglin
Adaptation
Physiological
Phenotype
Up-Regulation
Vascular contractility
Female
Inflammation Mediators
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Aortic Diseases
Mice
Transgenic
Diet
High-Fat
Nitric Oxide
Proinflammatory cytokine
03 medical and health sciences
Internal medicine
otorhinolaryngologic diseases
medicine
Animals
Humans
Genetic Predisposition to Disease
Inflammation
Dose-Response Relationship
Drug
Atherosclerosis
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Endocrinology
Fat diet
Mice
Inbred CBA
Biomarkers
Oxidative stress
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1423-0135
1018-1172
DOI: 10.1159/000448996
Popis: 14 p.-6 fig.
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.
The work was supported by grants from Czech Science Foundation GACR No. GA15-24015S, the Grant Agency of Charles University in Prague No. 1284214/C, No. 1158413C and SVV/2016/260293, the European Regional Development Fund under the Innovative Economy Program of the European Union (grant coordinated by JCET-UJ, No. POIG.01.01.02-00-069/09), the Ministerio de Economia y Competitividad of Spain (SAF2013-43421-R to C.B. and SAF2013-45784-R to J.M.L.-N.), the Junta de Castilla y Leon (GR100 to J.M.L.-N.), CIBERER (to C.B.) and Red de Investigación Cooperativa en Enfermedades Renales (REDINREN, RD12/0021/0032 to J.M.L.-N.). CIBERER and REDINREN are initiatives of the Instituto de Salud Carlos III of Spain supported by European Regional Development Funds (FEDER). The Cardiovascular Phenotyping Unit of the University of Salamanca received the support of FEDER.
Databáze: OpenAIRE
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