title: High soluble endoglin levels do not induce changes in structural parameters of mouse heart.
abstract: A soluble form of endoglin (sEng) released into the circulation was suggested to be a direct inducer of endothelial dysfunction, inflammation and contributed to the development of hypertension by interfering with TGF-β signaling in cardiovascular pathologies. In the present study, we assessed the hypothesis that high sEng level-induced hypertension via a possible sEng interference with TGF-β signaling pathways may result in inflammatory, structural or fibrotic changes in hearts of Sol-Eng+ mice (mice with high levels of soluble endoglin) fed either chow or high-fat diet. Female Sol-Eng+ mice and their age matched littermates with low plasma levels of sEng were fed either chow or high-fat diet (HFD). Heart samples were subsequently analyzed by histology, qRT-PCR and Western blot analysis. In this study, no differences in myocardial morphology/hypertrophy and possible fibrotic changes between Sol-Eng+ mice and control mice were detected on both chow and HFD. The presence of sEng did not significantly affect the expression of selected members of TGF-β signaling (membrane endoglin, TGFβRII, ALK-5, ALK-1, Id-1, PAI-1 and activated Smad proteins-pSmad 1,5 and pSmad 2,3), inflammation, heart remodeling (PDGFb, Col1A1) and endothelial dysfunction (VCAM-1, ICAM-1) in the hearts of Sol-Eng+ mice compared to control mice on both chow and high-fat diet. High levels of soluble endoglin did not affect microscopic structure (profibrotic and degenerative cardiomyocyte changes), and specific parts of TGF-β signaling, endothelial function and inflammation in the heart of Sol-Eng+ mice fed both chow diet or HFD. However, we cannot rule out a possibility that a long-term chronic exposure (9 months and more) to soluble endoglin alone or combined with other cardiovascular risk factors may contribute to alterations of heart function and structure in Sol-Eng+ mice, which is the topic in our lab in ongoing experiments.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Rathouska
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Fikrova
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 38, Hradec Kralove, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Mrkvicova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Blazickova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Michala
authors.initials: M
authors.lastname: Varejckova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Dolezelova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Nemeckova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Vitverova
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Peslova
authors.affiliation: Center for Biological Research, Spanish National Research Council (CSIC), and Biomedical Research Networking Center on Rare Diseases (CIBERER), 28040, Madrid, Spain.
authors.forename: Eunate
authors.initials: E
authors.lastname: Gallardo-Vara
authors.affiliation: Department of Physiology and Pharmacology, Renal and Cardiovascular Physiopathology Unit, University of Salamanca, 37007, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pericacho
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic. Petr.Nachtigal@faf.cuni.cz.
authors.forename: Petr
authors.identifier: http://orcid.org/0000-0001-9568-7295
authors.initials: P
authors.lastname: Nachtigal
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D000071063:Endoglin / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart; D006973:Hypertension / Q000097:blood* / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D016212:Transforming Growth Factor beta; D012313:RNA
keywords: Heart; Inflammation; Mice; Soluble endoglin; TGF-β signaling