title: Serine and metalloprotease signaling through PAR1 in arterial thrombosis and vascular injury.
abstract: Thrombin-dependent platelet activation has been shown to be important in the setting of angioplasty and stenting, which may cause ischemic complications including acute myocardial infarction and death. Inhibitors of the high-affinity thrombin receptor, protease-activated receptor 1 (PAR1), are now being evaluated in clinical trials for safety and efficacy in patients with atherothrombotic disease. However, it is unknown whether chronic inhibition of PAR1 in these large patient populations will have beneficial or possibly adverse effects on other biologic processes involved in blood vessel homeostasis and the response to vascular injury. Most recently, PAR1 was found to be cleaved at a distinct site by matrix metalloprotease-1 (MMP-1) to create a longer tethered ligand, which activates a distinct spectrum of G protein pathways in platelets. The differential activation by serine proteases such as thrombin and the metalloprotease MMP-1, places the protease receptor PAR1 at the junction of two major protease classes critically involved in thrombosis, matrix remodeling, and the response to vascular injury.
authors.affiliation: Hemostasis and Thrombosis Laboratory, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koukos
authors.forename: Leila
authors.initials: L
authors.lastname: Sevigny
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Lidija
authors.initials: L
authors.lastname: Covic
authors.forename: Athan
authors.initials: A
authors.lastname: Kuliopulos
mesh_terms: D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D057057:Serine Proteases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*; D057772:Vascular System Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D044463:Receptor, PAR-1; D045726:Metalloproteases; D057057:Serine Proteases