OBJECTIVE: Factor VII activating protease (FSAP) is a novel regulator of vascular inflammation and hemostasis. However, the molecular mechanism by which circulating FSAP influences inflammatory events and progression of atherosclerosis is not yet entirely understood. Here we have investigated the influence of FSAP on monocyte/macrophage functions. METHODS: We stimulated human monocyte-derived macrophages with FSAP and analyzed their cellular responses. RESULTS: FSAP induced IκB-dependent NF-κB activation in a time- and concentration-dependent fashion. FSAP also activated the phosphorylation and proteolytic degradation of the inhibitor protein IκBα. The phosphorylation of the p65 subunit of NF-κB was induced by FSAP, which is known to contribute to the enhancement of DNA-binding activity of NF-κB. Concomitantly, FSAP up-regulated the expression of pro-inflammatory cytokines, matrix metalloproteinases, cell adhesion molecules and tissue factor. In the presence of FSAP there was increased monocytes adhesion and transendothelial migration in a beta2 integrin dependent manner. CONCLUSIONS: Our findings suggest that FSAP activates the NF-κB pathway and the associated downstream pro-inflammatory factors in monocytic cells. This adds to a spectrum of FSAP effects on the vascular system that may explain its association with cardiovascular diseases.
OBJECTIVE:Factor VII activating protease (FSAP) is a novel regulator of vascular inflammation and hemostasis. However, the molecular mechanism by which circulating FSAP influences inflammatory events and progression of atherosclerosis is not yet entirely understood. Here we have investigated the influence of FSAP on monocyte/macrophage functions. METHODS: We stimulated human monocyte-derived macrophages with FSAP and analyzed their cellular responses. RESULTS:FSAP induced IκB-dependent NF-κB activation in a time- and concentration-dependent fashion. FSAP also activated the phosphorylation and proteolytic degradation of the inhibitor protein IκBα. The phosphorylation of the p65 subunit of NF-κB was induced by FSAP, which is known to contribute to the enhancement of DNA-binding activity of NF-κB. Concomitantly, FSAP up-regulated the expression of pro-inflammatory cytokines, matrix metalloproteinases, cell adhesion molecules and tissue factor. In the presence of FSAP there was increased monocytes adhesion and transendothelial migration in a beta2 integrin dependent manner. CONCLUSIONS: Our findings suggest that FSAP activates the NF-κB pathway and the associated downstream pro-inflammatory factors in monocytic cells. This adds to a spectrum of FSAP effects on the vascular system that may explain its association with cardiovascular diseases.
Authors: Mariana S Parahuleva; Bernhard Schieffer; Michael Klassen; Michael Worsch; Behnoush Parviz; Hans Hölschermann Journal: Med Sci Monit Date: 2018-06-21
Authors: Yu-Ching Cheng; Tara M Stanne; Anne-Katrin Giese; Weang Kee Ho; Matthew Traylor; Philippe Amouyel; Elizabeth G Holliday; Rainer Malik; Huichun Xu; Steven J Kittner; John W Cole; Jeffrey R O'Connell; John Danesh; Asif Rasheed; Wei Zhao; Stefan Engelter; Caspar Grond-Ginsbach; Yoichiro Kamatani; Mark Lathrop; Didier Leys; Vincent Thijs; Tiina M Metso; Turgut Tatlisumak; Alessandro Pezzini; Eugenio A Parati; Bo Norrving; Steve Bevan; Peter M Rothwell; Cathie Sudlow; Agnieszka Slowik; Arne Lindgren; Matthew R Walters; Jim Jannes; Jess Shen; David Crosslin; Kimberly Doheny; Cathy C Laurie; Sandip M Kanse; Joshua C Bis; Myriam Fornage; Thomas H Mosley; Jemma C Hopewell; Konstantin Strauch; Martina Müller-Nurasyid; Christian Gieger; Melanie Waldenberger; Annette Peters; Christine Meisinger; M Arfan Ikram; W T Longstreth; James F Meschia; Sudha Seshadri; Pankaj Sharma; Bradford Worrall; Christina Jern; Christopher Levi; Martin Dichgans; Giorgio B Boncoraglio; Hugh S Markus; Stephanie Debette; Arndt Rolfs; Danish Saleheen; Braxton D Mitchell Journal: Stroke Date: 2016-01-05 Impact factor: 7.914
Authors: M Olsson; T M Stanne; A Pedersen; E Lorentzen; E Kara; A Martinez-Palacian; N P Rønnow Sand; A F Jacobsen; P M Sandset; J J Sidelmann; G Engström; O Melander; S M Kanse; C Jern Journal: J Thromb Haemost Date: 2018-08-24 Impact factor: 5.824