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.

Center for Biological Research Spanish National Research Council 28040 Madrid Spain

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

Department of Medical Biochemistry Faculty of Medicine in Hradec Kralove Charles University Simkova 870 500 38 Hradec Kralove Czech Republic

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

Zobrazit více v PubMed

PLoS One. 2015 Mar 13;10 (3):e0119665 PubMed

Heart Vessels. 2017 May;32(5):628-636 PubMed

Nat Med. 2006 Jun;12 (6):642-9 PubMed

Int J Clin Exp Pathol. 2013 Dec 15;7(1):16-27 PubMed

Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H959-74 PubMed

Methods. 2001 Dec;25(4):402-8 PubMed

J Vasc Res. 2016;53(3-4):149-162 PubMed

BMC Med. 2010 Dec 20;8:86 PubMed

Circulation. 2012 Nov 27;126(22):2612-24 PubMed

Circulation. 2012 Jun 5;125(22):2728-38 PubMed

Cell Mol Life Sci. 2016 Apr;73(8):1715-39 PubMed

Curr Mol Med. 2013 Sep;13(8):1345-57 PubMed

Braz J Med Biol Res. 2000 Jun;33(6):693-700 PubMed

Mol Nutr Food Res. 2015 Mar;59(3):520-32 PubMed

Blood. 2013 Jan 10;121(2):403-15 PubMed

Heart Vessels. 2017 May;32(5):549-557 PubMed

Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1185-92 PubMed

J Cell Mol Med. 2008 Jun;12 (3):955-61 PubMed

Placenta. 2014 Feb;35 Suppl:S93-9 PubMed

Angiogenesis. 2016 Apr;19(2):155-71 PubMed

Genes Dev. 2008 May 15;22(10):1276-312 PubMed

Circulation. 2004 Sep 7;110(10 ):1263-8 PubMed

Basic Res Cardiol. 2014;109 (6):443 PubMed

Adv Gerontol. 2013;26(1):130-6 PubMed

Atherosclerosis. 1996 Feb;120(1-2):221-6 PubMed

Atherosclerosis. 2015 Dec;243(2):383-8 PubMed

Mini Rev Med Chem. 2012 Feb;12(2):175-83 PubMed

Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts