Factor VII-activating protease (FSAP): vascular functions and role in atherosclerosis.
FSAP is a plasma serine protease for which a potential role in the regulation of coagulation and fibrinolysis is postulated, based on its property to activate factor VII (FVII) as well as pro-urokinase (uPA). In clinical studies, the G534E single nucleotide polymorphism (Marburg I) of FSAP has been linked to late complications of atherothrombosis and is associated with a low proteolytic activity, particularly, towards pro-uPA. This has stimulated much interest in a search for additional functions of FSAP in the cardiovascular system. FSAP is a potent inhibitor of vascular smooth muscle cell proliferation and migration in vitro and local application of FSAP (but not Marburg I variant) in animal models reduces neointima formation. This is due to a reduced proteolytic activity of the variant isoform towards platelet derived growth factor-BB, a key mediator of neointima development. Moreover, appreciable quantities of FSAP are localized to unstable atherosclerotic plaques and may contribute to plaque instability. These data indicate that the cellular regulatory effects of FSAP may be more important than its influence on haemostasis. In this review the contribution of FSAP to vascular fibroproliferative inflammatory diseases in the context of pericellular proteolysis of the extracellular matrix, growth factor activity and haemostasis will be highlighted.
Kanse
Sandip M
SM
Department of Biochemistry, Medical School, Justus-Liebig-University, Friedrichstrasse 24, Giessen, Germany. sandip.kanse@biochemie.med.uni-giessen.de.
Parahuleva
Mariana
M
Muhl
Lars
L
Kemkes-Matthes
Bettina
B
Sedding
Daniel
D
Preissner
Klaus T
KT
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000077214:Becaplermin; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000201:enzymology; D005167:Factor VII / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006487:Hemostasis; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020574:Proto-Oncogene Proteins c-sis; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000201:enzymology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005167:Factor VII; C520095:FSAP protein, mouse; C433550:HABP2 protein, human; D012697:Serine Endopeptidases