Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix.

Abstract:

:Matrix metalloproteinase (MMP)-2 belongs to a family of zinc-dependent proteases which are best known for their ability to proteolyse extracellular matrix proteins throughout the body, including the cardiovascular system. Increased MMP-2 activity has been demonstrated in myocardial ischaemia and reperfusion injury and the progression to congestive heart failure, with most evidence to date for its role in cardiac remodelling. Recent evidence, however, shows that MMP-2 also co-localizes with and proteolyses specific protein targets within the cardiomyocyte to cause acute, reversible contractile dysfunction, challenging the conventional wisdom on the 'extracellular matrix only' actions of this enzyme. In this review, we discuss the recent upsurge in MMP-2 research with regards to its activation by non-proteolytic pathways in the setting of enhanced oxidative stress in the heart. We will focus on the consequences of intracellular actions of MMP-2 within the cardiomyocyte and its regulation at several levels including its expression, post-translational modifications, and regulation by endogenous tissue inhibitors of metalloproteinases, caveolin, and small molecule MMP inhibitors. MMP-2 is emerging as an important signalling protease implicated in the proteolytic regulation of various intracellular proteins in myocardial oxidative stress injury.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Kandasamy AD,Chow AK,Ali MA,Schulz R

doi

10.1093/cvr/cvp268

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

413-23

issue

3

eissn

0008-6363

issn

1755-3245

pii

cvp268

journal_volume

85

pub_type

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