Clearance of plasmin-PN-1 complexes by vascular smooth muscle cells in human aneurysm of the ascending aorta

Clearance of plasmin-PN-1 complexes by vascular smooth muscle cells in human aneurysm of the ascending aorta

Author Boukais, Kamel Google Scholar
Borges, Luciano F. Autor UNIFESP Google Scholar
Venisse, Laurence Google Scholar
Touat, Ziad Google Scholar
Francois, Deborah Google Scholar
Arocas, Veronique Google Scholar
Jondeau, Guillaume Google Scholar
Declerck, Paul Google Scholar
Bouton, Marie-Christine Google Scholar
Michel, Jean-Baptiste Google Scholar
Abstract Plasminogen is a circulating zymogen which enters the arterial wall by radial, transmural hydraulic conductance, where it is converted to plasmin by tissue plasminogen activator t-PA on an activation platform involving S100A4 on the vascular smooth muscle cell (vSMC) membrane. Plasmin is involved in the progression of human thoracic aneurysm of the ascending aorta (TAA), vSMCs protect the TM wall from plasmin-induced proteolytic injury by expressing high levels of antiproteases. Protease nexin-1 (PN-1) is a tissue antiprotease belonging to the serpin superfamily, expressed in the vascular wall, and is able to form a covalent complex with plasmin. LDL receptor related protein-1 (LRP-1) is a scavenger receptor implicated in protease-antiprotease complex internalization. In this study, we investigated whether PN-1 and LRP-1 are involved in the inhibition and clearance of plasminogen by the SMCs of human TAA. We demonstrated an overexpression of S100A4, PN-1, and LRP-1 in the medial layer of human TM. Plasminogen activation taking place in the media of TAA was revealed by immunohistochemical staining and plasmin activity analyses. We showed by cell biology studies that plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs from healthy and TAA media. Thus, two complementary mechanisms are involved in the protective role of PN-1 in human TM: one involving plasmin inhibition and the other involving tissue clearance of plasmin-PN1 complexes via the scavenger receptor LRP-1. (C) 2017 Elsevier Inc. All rights reserved.
Keywords Proteases
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor INSERM, Paris Diderot University
French National Research Agency
Grant number French National Research Agency: ANR-14-CE 15-0012-03
French National Research Agency: ANR-BSV1-0009-01
Date 2018
Published in Cardiovascular Pathology. New York, v. 32, p. 15-25, 2018.
ISSN 1054-8807 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Inc
Extent 15-25
Access rights Closed access
Type Article
Web of Science ID WOS:000419095700003

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