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

Autor: Hazell GG; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., Peachey AM; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., Teasdale JE; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., Sala-Newby GB; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., Angelini GD; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., Newby AC; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK., White SJ; School of Clinical Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.; School of Healthcare Science, Manchester Metropolitan University, John Dalton Building, Manchester M1 5GD, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 Dec 20; Vol. 6, pp. 39553. Date of Electronic Publication: 2016 Dec 20.
DOI: 10.1038/srep39553
Abstrakt: 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.
Databáze: MEDLINE
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