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
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