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(Hypertension. 2006;48:830.)
© 2006 American Heart Association, Inc.

Editorial Commentary

Digesting the Remodeled Heart

Role of Lysosomal Cysteine Proteases in Heart Failure

Flora Sam; Deborah A. Siwik

From the Whitaker Cardiovascular Institute, Boston University School of Medicine, Mass.

Correspondence to Flora Sam, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St, Room X704, Boston, MA 02118. E-mail flora.sam@bmc.org

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

Of the many proteinases present in the myocardium, members of the matrix metalloproteinase (MMP) family have received most attention. However, the cysteine proteases and their inhibitors have now been implicated in the pathogenesis of cardiac remodeling in the hypertrophied and failing heart. Cathepsins, cysteine proteases of the papain family, are optimally active in the acidic pH of lysosomes and are responsible for the physiological digestive turnover of cellular molecules and organelles. We now know that the levels of cathepsins and their endogenous inhibitors, cystatins, can be regulated by a number of signaling molecules, and cathepsins can be released from lysosomes into the extracellular space. Cysteine proteinases may degrade extracellular matrix proteins, such as elastin and fibrillar collagens.¹ Nonlysosomal cathepsin targets include degradation of matrix and bone via elastinolytic/collagenolytic activity, activation of pro-MMP, induction of anoikis-dependent apoptosis via matrix degradation, activation of caspases, and cleavage of focal adhesion kinases. A decade ago, measurement of cathepsin activity in heart tissue of different pathologies was used as a measure of lysosomal activity and integrity. Now, as in the article by Cheng et al² in this issue of Hypertension, regulated cathepsin release and activity is believed to be an important mediator of cardiac remodeling.

In human dilated cardiomyopathy heart tissue, cathepsin B mRNA and expression is increased compared with control hearts.³ Cathepsin B can activate urokinase-plasminogen activator (serine proteases) ultimately leading to activation of MMP activity. However, cathepsin B activity is very low at neutral pH. Work in macrophages⁴ has demonstrated that regulated . . . [Full Text of this Article]

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