Elsevier

Matrix Biology

Volume 74, December 2018, Pages 21-34
Matrix Biology

SPARC preserves endothelial glycocalyx integrity, and protects against adverse cardiac inflammation and injury during viral myocarditis

https://doi.org/10.1016/j.matbio.2018.04.015Get rights and content
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Highlights

  • The vascular glycocalyx is an extracellular matrix that regulates inflammation in the heart.

  • Absence of glycoprotein SPARC compromises the integrity of the endothelial glycocalyx.

  • Compromised glycocalyx is shown using intra-vital microscopy and electron microscopy.

  • Restoring the glycocalyx with exogenous SPARC improves the outcome in viral myocarditis.

Abstract

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.

Keywords

SPARC
Endothelial glycocalyx
Viral myocarditis
Extracellular matrix
Inflammation

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Contributed equally.