SPARC preserves endothelial glycocalyx integrity, and protects against adverse cardiac inflammation and injury during viral myocarditis
Autor: | Bianca Hemmeryckx, Elizabeth A. V. Jones, Wouter Verhesen, Rick van Leeuwen, Jurgen W. G. E. van Teeffelen, Anna-Pia Papageorgiou, Marieke Rienks, Daniel M. Johnson, Stephane Heymans, Bart Eskens, Paolo Carai |
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Přispěvatelé: | RS: CARIM - R2 - Cardiac function and failure, Promovendi CD, Cardiologie, RS: CARIM - R2.02 - Cardiomyopathy, Fysiologie, CTC, RS: CARIM - R2.12 - Surgical intervention, MUMC+: MA Med Staf Spec Cardiologie (9) |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Pathology Viral Myocarditis Angiogenesis ANGIOGENESIS ACTIVATION Gene Knockout Techniques Mice Viral myocarditis Medicine FIBROSIS Osteonectin Abdominal Muscles DIASTOLIC FUNCTION ROLE Cardiac muscle Extracellular matrix Enterovirus B Human FIBRILLAR COLLAGEN CONTENT Myocarditis medicine.anatomical_structure Systemic administration medicine.symptom Life Sciences & Biomedicine medicine.medical_specialty Biochemistry & Molecular Biology Coxsackievirus Infections Hyaluronoglucosaminidase Inflammation Glycocalyx 03 medical and health sciences PHENOTYPIC HETEROGENEITY AGE PRESSURE-OVERLOAD EXTRACELLULAR-MATRIX Animals Molecular Biology Pressure overload HEPARAN-SULFATE Science & Technology business.industry SPARC Cell Biology medicine.disease Endothelial glycocalyx Disease Models Animal Microscopy Electron 030104 developmental biology business |
Zdroj: | Matrix Biology, 74, 21-34. Elsevier Science Rienks, M, Carai, P, van Teeffelen, J, Eskens, B, Verhesen, W, Hemmeryckx, B, Johnson, D M, van Leeuwen, R, Jones, E A, Heymans, S & Papageorgiou, A-P 2018, ' SPARC preserves endothelial glycocalyx integrity, and protects against adverse cardiac inflammation and injury during viral myocarditis ', Matrix Biology . https://doi.org/10.1016/j.matbio.2018.04.015 |
ISSN: | 0945-053X |
Popis: | Myocardial damage as a consequence of cardiotropic viruses leads to a broad variety of clinical presentations and is still a complicated condition to diagnose and treat. Whereas the extracellular matrix protein Secreted Protein Acidic and Rich in Cysteine or SPARC has been implicated in hypertensive and ischemic heart disease by modulating collagen production and cross-linking, its role in cardiac inflammation and endothelial function is yet unknown. Absence of SPARC in mice resulted in increased cardiac inflammation and mortality, and reduced cardiac systolic function upon coxsackievirus-B3 induced myocarditis. Intra-vital microscopic imaging of the microvasculature of the cremaster muscle combined with electron microscopic imaging of the microvasculature of the cardiac muscle uncovered the significance of SPARC in maintaining endothelial glycocalyx integrity and subsequent barrier properties to stop inflammation. Moreover, systemic administration of recombinant SPARC restored the endothelial glycocalyx and consequently reversed the increase in inflammation and mortality observed in SPARC KO mice in response to viral exposure. Reducing the glycocalyx in vivo by systemic administration of hyaluronidase, an enzyme that degrades the endothelial glycocalyx, mimicked the barrier defects found in SPARC KO mice, which could be restored by subsequent administration of recombinant SPARC. In conclusion, the secreted glycoprotein SPARC protects against adverse cardiac inflammation and mortality by improving the glycocalyx function and resulting endothelial barrier function during viral myocarditis. ispartof: MATRIX BIOLOGY vol:74 pages:21-34 ispartof: location:Netherlands status: published |
Databáze: | OpenAIRE |
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