Targeted subendothelial matrix oxidation by myeloperoxidase triggers myosin II-dependent de-adhesion and alters signaling in endothelial cells.

ABSTRACT: During inflammation, myeloperoxidase (MPO) released by circulating leukocytes accumulates within the subendothelial matrix by binding to and transcytosing the vascular endothelium. Oxidative reactions catalyzed by subendothelial-localized MPO are implicated as a cause of endothelial dysfunction in vascular disease. While the subendothelial matrix is a key target for MPO-derived oxidants during disease, the implications of this damage for endothelial morphology and signaling are largely unknown. We found that endothelial-transcytosed MPO produced hypochlorous acid (HOCl) that reacted locally with the subendothelial matrix and induced covalent cross-linking of the adhesive matrix protein fibronectin. Real-time biosensor and live cell imaging studies revealed that HOCl-mediated matrix oxidati

SUBMITTER: Rees MD 

PROVIDER: S-EPMC3529214 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature