Matrix metalloproteinase-9 expression after myocardial infarction: physiological or pathological?
Authors: M. M. Thompson, I. B. Squire
Journal: Cardiovascular Research (2002)

See article by Romanic et al. [24] ( pages 549 -558) incomposition of the vasculature are the collagenases and this issue.gelatinases.The collagenases (MMP-1, -8 and -13) have the ability to cleave collagen types I-III.The gelatinases Remodelling of the extracellular matrix is acknowledged (MMP-2, -9, -12) have broader substrate specificity for to play a significant role in a number of vascular disorders type IV collagen, elastin, aggrecan and vitronectin, but including aneurysm formation, rupture of atherosclerotic may degrade other elements of the extracellular matrix, plaques, and development of intimal hyperplasia [1,2].In including interstitial collagen [7], to varying degrees.recent years, investigations of matrix biology have been (reviews of MMPs [4,5]).applied to cardiac remodelling following acute myocardial infarction (MI).Left ventricular dilatation following MI is related to the extent of the ischaemic insult and subsequent 1.Expression of MMPs following MI healing of the infarct and surrounding tissue [3].Whilst the process of postinfarct remodelling is incompletely under-The effect of myocardial ischaemia and reperfusion on stood, excessive degradation of extracellular matrix com-MMP expression has been studied experimentally.Utilisponents appears to result in pathological cardiac remodel-ing a rodent model, Peterson et al.[8] reported a differenling, left ventricular dilatation and cardiac failure.tial time course of MMP expression following experimen-The major physiological regulators of the extracellular tal infarction.In this study, the major rodent collagenases matrix are the matrix metalloproteinases (MMP), which and gelatinases (MMP-2, -9, -13) increased in the first have been implicated in the genesis of postinfarct ventricu-week following coronary occlusion, whilst MMP-8 and -14 lar failure [6].The MMPs are a family of structurally (membrane type MMP-1) only became elevated when related endopeptidases that have the ability to degrade all heart failure occurred.The time course of MMP-9 induccomponents of the extracellular matrix.The MMPs are tion was further investigated by Romanic et al. [9], who classified according to their substrate specificity and demonstrated that MMP-9 was upregulated within 24 h of presence of a transmembrane domain (collagenases, MI and that this rise was accompanied by a reduction in gelatinases, stromelysins and membrane type).The en-the physiological inhibitor of MMP-9, TIMP-1.Several zymes all share a degree of structural homology, contain a other investigators have since revealed that MMP-9 is zinc atom at the catalytic site, and are inhibited by specific expressed within minutes of myocardial ischaemia [10,11], inhibitors (tissue inhibitors of matrix metalloproteinases-and that the increased MMP-9 appears to be neutrophil TIMP).Most MMPs require activation by proteolytic derived and in the active form [12]. cleavage, and several serine proteases, particularly plas-Compelling experimental data have suggested that a min, play an important role in this process.spectrum of MMPs are overexpressed at different time The most important MMPs with respect to the matrix periods following MI.The apparent implication of these observations was that MMP driven proteolysis might affect myocardial function following ischaemia, with respect to