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(Hypertension. 2006;47:640.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Matrix Reloaded

The Matrix Metalloproteinase Paradox

Anna N. Panek; Michael Bader

From the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.

Correspondence to Michael Bader, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany. E-mail mbader@mdc-berlin.de

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Chronic hypertension leads to adaptive processes in the heart, called remodeling, which are characterized by hypertrophic changes of cardiomyocytes and by structural alterations of the extracellular matrix. Although these processes are initially compensatory and preserve cardiac contractile performance, they finally lead to left ventricular (LV) dilatation and heart failure. Thus, factors playing a crucial role in remodeling are promising therapeutic targets.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are intimately involved in extracellular matrix remodeling. This family of >20 endopeptidases consists of collagenases (such as MMP-1 and MMP-13), stromelysins (MMP-3), and gelatinases (MMP-2 and MMP-9).¹ The activity of MMPs is controlled by endogenous inhibitors called tissue inhibitors of metalloproteinases (TIMPs).

MMP-2 and MMP-9 are expressed by a multitude of cell types including cardiac myocytes and fibroblasts. It was reported that both enzymes are highly upregulated in hypertrophic and failing hearts, and they have been implicated in the progression of ventricular dilatation and the development of heart failure. However, MMP-2 and MMP-9 degrade type IV and V collagens, fibronectin, gelatins, laminin, and elastin, proteins that are accumulating in the damaged myocardium undergoing fibrosis. Thus, it is not clear whether MMPs are involved in the pathogenetic process of fibrosis or whether their upregulation represents a vain compensatory reaction.

In the current issue of Hypertension, Matsusaka et al² evaluate effects of MMP-2 on structural and functional alterations of the left ventricle during cardiac hypertrophy because of pressure overload induced by transverse aortic constriction. They used an MMP-2 knockout (KO) mouse model, which . . . [Full Text of this Article]

Related Article:

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

Hidenori Matsusaka, Tomomi Ide, Shouji Matsushima, Masaki Ikeuchi, Toru Kubota, Kenji Sunagawa, Shintaro Kinugawa, and Hiroyuki Tsutsui
Hypertension 2006 47: 711-717. [Abstract] [Full Text] [PDF]

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