Targeted Deletion of Matrix Metalloproteinase 2 Ameliorates Myocardial Remodeling in Mice With Chronic Pressure Overload

Matrix metalloproteinases (MMPs) play an important role in the extracellular matrix remodeling. Experimental and clinical studies have demonstrated that MMP 2 and 9 are upregulated in the dilated failing hearts and involved in the development and progression of myocardial remodeling. However, little...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2006-04, Vol.47 (4), p.711-717
Main Authors: Matsusaka, Hidenori, Ide, Tomomi, Matsushima, Shouji, Ikeuchi, Masaki, Kubota, Toru, Sunagawa, Kenji, Kinugawa, Shintaro, Tsutsui, Hiroyuki
Format: Article
Language:English
Subjects:
Animals
Aorta
Cardiomegaly - diagnostic imaging
Cardiomegaly - etiology
Cardiomegaly - pathology
Chronic Disease
Collagen - metabolism
Constriction, Pathologic
Echocardiography
Fibrosis
Gene Deletion
Hemodynamics
Hypertension - complications
Hypertension - genetics
Hypertension - physiopathology
Lung - pathology
Male
Matrix Metalloproteinase 2 - genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium - pathology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Organ Size - drug effects
RNA, Messenger - metabolism
Ventricular Remodeling
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Summary:Matrix metalloproteinases (MMPs) play an important role in the extracellular matrix remodeling. Experimental and clinical studies have demonstrated that MMP 2 and 9 are upregulated in the dilated failing hearts and involved in the development and progression of myocardial remodeling. However, little is known about the role of MMPs in mediating adverse myocardial remodeling in response to chronic pressure overload (PO). We, thus, hypothesized that selective disruption of the MMP 2 gene could ameliorate PO-induced cardiac hypertrophy and dysfunction in mice. PO hypertrophy was induced by transverse aortic constriction (TAC) in male MMP 2 knockout (KO) mice (n=10) and sibling wild-type (WT) mice (n=9). At 6 weeks, myocardial MMP 2 zymographic activity was 2.4-fold increased in WT+TAC, and this increase was not observed in KO+TAC, with no significant alterations in other MMPs (MMP 1, 3, 8, and 9) or tissue inhibitors of MMPs (1, 2, 3, and 4). TAC resulted in a significant increase in left ventricular (LV) weight and LV end-diastolic pressure (EDP) with preserved systolic function. KO+TAC mice exerted significantly lower LV weight/body weight (4.2±0.2 versus 5.0±0.2 mg/g; P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000208840.30778.00