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Heparan Sulfate Modulates Heart Vascular Remodeling Induced by S. Aureus Sepsis
Author(s) -
Morris Claire L.,
Golden Greg,
Toledo Alejandro Gomez,
Esko Jeffrey D.,
Nizet Victor
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07339
Subject(s) - sepsis , heparan sulfate , glycocalyx , staphylococcus aureus , immunology , biology , medicine , biochemistry , bacteria , cell , genetics
Sepsis is a life‐threatening condition triggered by a dysregulated host response to microbial infection resulting in vascular dysfunction and organ failure. Infection by Staphylococcus aureus infections can result in sepsis, which is correlated with remodeling of the vascular glycocalyx. Heparan sulfate (HS), a major component of the vascular glycocalyx, undergoes shedding during sepsis, but the impact of vascular HS and shedding on sepsis outcomes is unknown. In this study, we modified the composition of HS in endothelia cells in mice by crossbreeding animals bearing a conditional allele in N‐acetylglucosamine N‐deacetylase‐N‐sulfotransferase‐1 ( Ndst1 f/f ) with mice bearing the Cre recombinase driven by the Tie2 promoter (Tie2‐Cre). Ndst1 f/f Tie2Cre mice exhibit HS with overall reduced sulfation in endothelial and myeloid cells. Ndst1 f/f Tie2Cre mice succumbed earlier to sepsis induced by S. aureus. Application of an in vivo vascular tagging method revealed drastic proteomic changes in the hearts of Ndst1 f/f Tie2Cre mice, including increased markers of cardiac damage. These studies provide a link between vascular heparan sulfate and early death due to S. aureus infection. Additional measures of characterizing cardiac damage will further explore the heart proteomics signature in Ndst1 f/f Tie2Cre mice to increased S. aureus susceptibility.