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PI16 is a shear stress and inflammation-regulated inhibitor of MMP2.

Scientific reports (2016-12-21)
Georgina G J Hazell, Alasdair M G Peachey, Jack E Teasdale, Graciela B Sala-Newby, Gianni D Angelini, Andrew C Newby, Stephen J White
ABSTRACT

Raised endothelial shear stress is protective against atherosclerosis but such protection may be lost at sites of inflammation. We found that four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells (HCAECs), in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β. Immunohistochemistry demonstrated that PI16 is expressed in human coronary endothelium and in a subset of neointimal cells and medial smooth muscle cells. Adenovirus-mediated PI16 overexpression inhibits HCAEC migration and secreted matrix metalloproteinase (MMP) activity. Moreover, PI16 inhibits MMP2 in part by binding an exposed peptide loop above the active site. Our results imply that, at high endothelial shear stress, PI16 contributes to inhibition of protease activity; protection that can be reversed during inflammation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-PI16 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-BrdU antibody, Mouse monoclonal, clone BU-33, purified from hybridoma cell culture
Sigma-Aldrich
ExtrAvidin®−Peroxidase, buffered aqueous solution
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution