Mariana S Parahuleva1, Sandip M Kanse2, Behnoush Parviz1, Andreas Barth1, Harald Tillmanns1, Rainer M Bohle3, Daniel G Sedding1, Hans Hölschermann4. 1. Internal Medicine I/Cardiology and Angiology, Justus-Liebig-University, Giessen, Germany. 2. Institute for Biochemistry, Justus-Liebig-University, Giessen, Germany. 3. Institute of General and Specialist Pathology, Homburg, Germany. 4. Hochtaunusklinik Internal Medicine I/Cardiology and Angiology, Urseler Straße 33, 61348 Bad Homburg, Germany. Electronic address: hans.hoelschermann@hochtaunus-kliniken.de.
Abstract
OBJECTIVE: The Factor Seven Activating Protease (FSAP) is known to influence fibrinolysis and to play a critical role in the inhibition of vascular smooth muscle cell (VSMC) proliferation and migration as well as neointima formation. In order to define the role of FSAP in vascular pathophysiology we have investigated the expression of FSAP protein and mRNA in human vascular cells and coronary atherosclerotic plaques with defined clinical features. METHODS AND RESULTS: Directional coronary atherectomy (DCA) specimens from 40 lesions were analyzed for FSAP antigen and mRNA expression. Higher level of FSAP mRNA (p<0.001) as well as FSAP immunostaining (p<0.005) was observed in patients with acute coronary syndromes compared to patients with stable angina pectoris. FSAP antigen was found to be focally accumulated in hypocellular and lipid-rich areas within the necrotic core of atherosclerotic plaques. FSAP was also co-localized with CD11b/CD68 expressing cells in macrophage-rich shoulder regions of the plaques. Monocyte-derived macrophages expressed FSAP in vitro and this was further induced by pro-inflammatory mediators. CONCLUSIONS: FSAP accumulation in coronary atherosclerotic lesions is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. The higher expression of FSAP in unstable plaques suggests that it may destabilize plaque through reducing VSMC proliferation/migration and altering the hemostatic balance.
OBJECTIVE: The Factor Seven Activating Protease (FSAP) is known to influence fibrinolysis and to play a critical role in the inhibition of vascular smooth muscle cell (VSMC) proliferation and migration as well as neointima formation. In order to define the role of FSAP in vascular pathophysiology we have investigated the expression of FSAP protein and mRNA in human vascular cells and coronary atherosclerotic plaques with defined clinical features. METHODS AND RESULTS: Directional coronary atherectomy (DCA) specimens from 40 lesions were analyzed for FSAP antigen and mRNA expression. Higher level of FSAP mRNA (p<0.001) as well as FSAP immunostaining (p<0.005) was observed in patients with acute coronary syndromes compared to patients with stable angina pectoris. FSAP antigen was found to be focally accumulated in hypocellular and lipid-rich areas within the necrotic core of atherosclerotic plaques. FSAP was also co-localized with CD11b/CD68 expressing cells in macrophage-rich shoulder regions of the plaques. Monocyte-derived macrophages expressed FSAP in vitro and this was further induced by pro-inflammatory mediators. CONCLUSIONS:FSAP accumulation in coronary atherosclerotic lesions is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. The higher expression of FSAP in unstable plaques suggests that it may destabilize plaque through reducing VSMC proliferation/migration and altering the hemostatic balance.
Authors: Mariana S Parahuleva; Sandip Kanse; Hans Hölschermann; Kirila Zheleva; Daniel Zandt; Michael Worsch; Behnoush Parviz; Norbert Güttler; Harald Tillmanns; Andreas Böning; Ali Erdogan Journal: J Thromb Thrombolysis Date: 2014-04 Impact factor: 2.300
Authors: Stella Trompet; Douwe Pons; Sandip M Kanse; Anton J M de Craen; M Arfan Ikram; Jeffrey J W Verschuren; Aeilko H Zwinderman; Pieter A F M Doevendans; René A Tio; Robbert J de Winter; P Eline Slagboom; Rudi G J Westendorp; J Wouter Jukema Journal: Stroke Res Treat Date: 2011-06-30
Authors: Birgit Markus; Karsten Grote; Michael Worsch; Behnoush Parviz; Andreas Boening; Bernhard Schieffer; Mariana S Parahuleva Journal: PLoS One Date: 2016-09-15 Impact factor: 3.240
Authors: Mariana S Parahuleva; Bernhard Schieffer; Michael Klassen; Michael Worsch; Behnoush Parviz; Hans Hölschermann Journal: Med Sci Monit Date: 2018-06-21
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