Your browser doesn't support javascript.
loading
Osteoglycin prevents the development of age-related diastolic dysfunction during pressure overload by reducing cardiac fibrosis and inflammation.
Deckx, Sophie; Heggermont, Ward; Carai, Paolo; Rienks, Marieke; Dresselaers, Tom; Himmelreich, Uwe; van Leeuwen, Rick; Lommen, Wies; van der Velden, Jolanda; Gonzalez, Arantxa; Diez, Javier; Papageorgiou, Anna-Pia; Heymans, Stephane.
Afiliação
  • Deckx S; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands; Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium.
  • Heggermont W; Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium.
  • Carai P; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands; Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium.
  • Rienks M; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands.
  • Dresselaers T; Biomedical MRI Unit, Department of Imaging and Pathology, KU Leuven, Belgium.
  • Himmelreich U; Biomedical MRI Unit, Department of Imaging and Pathology, KU Leuven, Belgium.
  • van Leeuwen R; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands.
  • Lommen W; Biomedical MRI Unit, Department of Imaging and Pathology, KU Leuven, Belgium.
  • van der Velden J; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
  • Gonzalez A; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Spain; CIBERCV, National Health Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
  • Diez J; Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Spain; CIBERCV, National Health Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
  • Papageorgiou AP; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands; Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium. Electronic address: anna.papageorgiou@maastrichtuniversity.nl.
  • Heymans S; Center for Heart Failure Research, Cardiovascular Research Institute Maastricht, The Netherlands; Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium; ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
Matrix Biol ; 66: 110-124, 2018 03.
Article em En | MEDLINE | ID: mdl-28958774
ABSTRACT
The small leucine-rich proteoglycan osteoglycin has been implicated in matrix homeostasis in different organs, including the ischemic heart. However, whether osteoglycin modulates cardiac hypertrophy, fibrosis or inflammation in hypertensive heart disease and during aging remains unknown. Angiotensin-II-induced pressure overload increases cardiac osteoglycin expression, concomitant with the onset of inflammation and extracellular matrix deposition. Interestingly aging led to decreased cardiac levels of osteoglycin, yet absence of osteoglycin did not affect organ structure or cardiac function up to the age of 18months. However, Angiotensin-II infusion in combination with aging resulted in exaggerated cardiac fibrosis and inflammation in the osteoglycin null mice as compared to wild-type mice, resulting in increased diastolic dysfunction as determined by magnetic resonance imaging. In vitro, stimulation of bone marrow derived macrophages from osteoglycin null mice with Angiotensin-II resulted in significantly higher levels of ICAM-1 as well as pro-inflammatory cytokines and chemokines IL-1ß and MCP-1 as compared to WT cells. Further, stimulation of human cardiac fibroblasts with osteoglycin reduced cell proliferation and inhibited TGF-ß induced collagen gene expression. In mouse cardiac tissue, osteoglycin expression inversely correlated with TGF-ß expression and in cardiac biopsies of aortic stenosis patients, osteoglycin expression is significantly higher than in control biopsies. Interestingly, osteoglycin levels were higher in patients with less severe myocardial fibrosis and overall in the aortic stenosis patients osteoglycin levels negatively correlated with collagen content in the myocardium. In conclusion, osteoglycin expression is increased in the heart in response to pressure overload and its absence results in increased cardiac inflammation and fibrosis resulting in increased diastolic dysfunction.
Assuntos
Palavras-chave

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Estenose da Valva Aórtica / Angiotensina II / Peptídeos e Proteínas de Sinalização Intercelular / Hipertensão / Miocárdio Limite: Animals / Humans Idioma: En Revista: Matrix Biol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Bélgica

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Estenose da Valva Aórtica / Angiotensina II / Peptídeos e Proteínas de Sinalização Intercelular / Hipertensão / Miocárdio Limite: Animals / Humans Idioma: En Revista: Matrix Biol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Bélgica