References
Query Results -- Details
MGI Accession ID: MGI:1100158
J Number: J:44387
Other Accession IDs:
Title: Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation.
Authors: Carmeliet P; Moons L; Lijnen R; Baes M; Lemaitre V; Tipping P; Drew A; Eeckhout Y; Shapiro S; Lupu F; Collen D
Journal: Nat Genet
Volume: 17
Issue: 4
Date: 1997 Dec
Year: 1997
Pages: 439-44
Review Status: Peer Reviewed
Abstract:
The molecular mechanisms predisposing to atherosclerotic aneurysm formation remain undefined. Nevertheless, rupture of aortic aneurysms is a major cause of death in Western societies, with few available treatments and poor long-term prognosis. Indirect evidence suggests that matrix metalloproteinases (MMPs) and plasminogen activators (PAs) are involved in its pathogenesis. MMPs are secreted as inactive zymogens (pro-MMPs), requiring activation in the extracellular compartment. Plasmin, generated from the zymogen plasminogen by tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA; refs 14,15), has been proposed as a possible activator in vitro, but evidence for such a role in vivo is lacking. Analysis of atherosclerotic aorta in mice with a deficiency of apoliprotein E (Apoe-/-; ref. 18), singly or combined with a deficiency of t-PA (Apoe-/-:Plat-/-) or of u-PA (Apoe-/-:Plau-/-; ref. 19), indicated that deficiency of u-PA protected against media destruction and aneurysm formation, probably by means of reduced plasmin-dependent activation of pro-MMPs. This genetic evidence suggests that plasmin is a pathophysiologically significant activator of pro-MMPs in vivo and may have implications for the design of therapeutic strategies to prevent aortic-wall destruction by controlling Plau gene function.
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