References
Query Results -- Details
MGI Accession ID: MGI:3525733
J Number: J:95236
Other Accession IDs:
Title: Loss or inhibition of uPA or MMP-9 attenuates LV remodeling and dysfunction after acute pressure overload in mice.
Authors: Heymans S; Lupu F; Terclavers S; Vanwetswinkel B; Herbert JM; Baker A; Collen D; Carmeliet P; Moons L
Journal: Am J Pathol
Volume: 166
Issue: 1
Date: 2005 Jan
Year: 2005
Pages: 15-25
Review Status: Peer Reviewed
Abstract:
Left ventricular (LV) hypertrophy is a natural response of the heart to increased pressure loading, but accompanying fibrosis and dilatation may result in irreversible life-threatening heart failure. Matrix metalloproteinases (MMPs) have been invoked in various cardiac diseases, however, direct genetic evidence for a role of the plasminogen activator (PA) and MMP systems in pressure overload-induced LV hypertrophy and in heart failure is lacking. Therefore, the consequences of transverse aortic banding (TAB) were analyzed in mice lacking tissue-type PA (t-PA(-/-)), urokinase-type PA (u-PA(-/-)), or gelatinase-B (MMP-9(-/-)), and in wild-type (WT) mice after adenoviral gene transfer of the PA-inhibitor PAI-1 or the MMP-inhibitor TIMP-1. TAB elevated LV pressure comparably in all genotypes. In WT and t-PA(-/-) mice, cardiomyocyte hypertrophy was associated with myocardial fibrosis, LV dilatation and dysfunction, and pump failure after 7 weeks. In contrast, in u-PA(-/-) mice or in WT mice after PAI-1- and TIMP-1-gene transfer, cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation, resulting in better preservation of pump function. Deficiency of MMP-9 had an intermediate effect. These findings suggest that the use of u-PA- or MMP-inhibitors might preserve cardiac pump function in LV pressure overloading.
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