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Mechanoregulation of extracellular matrix dynamics by endothelial cell surface heparan sulfate
Author(s) -
Helmke Brian P.,
Qian Jessie J.,
Mott Rosalind E.
Publication year - 2009
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.23.1_supplement.951.4
Subject(s) - heparan sulfate , fibronectin , extracellular matrix , glycocalyx , chemistry , heparanase , biophysics , perlecan , laminin , fibril , colocalization , microbiology and biotechnology , matrix (chemical analysis) , biochemistry , heparin , biology , chromatography
Decentralized mechanotransmission through endothelial cells (ECs) induces rapid fibronectin (Fn) fibril remodeling in response to hemodynamic shear stress, but mechanisms regulating adaptation of extracellular matrix structure are poorly understood. Since heparan sulfate in the glycocalyx has been proposed to modulate mechanosignaling at the apical cell surface, we hypothesized that it also contributes to mechanotransmission from the basal surface to Fn. Heparan sulfate in primary cultured post‐confluent EC monolayers was primarily in the subendothelial matrix. Heparinase pretreatment decreased initial displacement rate and eliminated directional displacement of Fn fibrils after flow onset. Competitive inhibition of heparan sulfate binding to Fn by heparin allowed coordinated fibril displacement but in random directions rather than in the flow direction. A C‐terminal Fn fragment containing HepII domains but not integrin binding domains reduced heparan sulfate expression but not colocalization with Fn fibrils. Displacement after flow onset remained in the downstream direction but became more heterogeneous, and displacement rate decreased significantly. Thus, heparan sulfate expression and association with Fn fibrils contribute to mechanoregulation of subendothelial matrix dynamics. Supported by NIH grants HL076499, HL071958, and HL080956.