Oxidative stress may play an important role in the regulation of MMP activity. Augmented MMP activity may be involved in the development of ventricular remodelling in patients with coronary artery disease.

No abstract

No abstract

eperfusion therapy, including percutaneous coronary intervention, reduces the mortality of patients with acute myocardial infarction (AMI), 1,2 but when AMI is complicated with cardiac rupture or ventricular septal perforation (VSP), the mortality rate is markedly increased. 3 Within a few days after the onset of AMI, proteases and reactive oxygen species are released from neutrophils infiltrating the infarcted cardiac tissue and these induce myocardial injury. 3,4 In an experimental AMI model, augmented activity of matrix metalloproteinase (MMP)-9, which is derived from neutrophils, was demonstrated in the infarcted area. 5-7 Furthermore, it was reported that knockout deletion of MMP-9 in mice prevented cardiac rupture complicating AMI. 7 These findings indicate that augmented MMP-9 activity derived from neutrophils may contribute to the development of cardiac rupture or VSP, but the pathophysiology in humans is unclear.By measuring the MMP activity and level of 8-isoprostagandin F2 (8-iso-PGF2 ) in the pericardial fluid (PF) in patients with coronary artery disease (CAD) undergoing coronary artery bypass graft surgery (CABG), we were able to recently report that cardiac MMP activity is related to ventricular remodeling and that oxidative stress Circulation Journal Vol.70, June 2006might play an important role in the regulation of MMP activity. 8 PF is considered to reflect not only the ultrafiltrate of the plasma, but also the transudate from the cardiac interstitium. 9 However, PF obtained from patients with freewall-type cardiac rupture is not suitable for investigating the cardiac interstitium because of considerable contamination with blood. Non-hemorrhagic PF can be obtained from patients with VSP because the pathogenesis is generally considered as almost identical to free wall cardiac rupture. 3 To clarify the role of neutrophil and MMP activity in the pathophysiology of AMI and cardiac rupture, we measured the concentrations of interleukin-8 (IL-8), a chemoattractant of neutrophils, 10 monocyte chemotactic protein-1 (MCP-1), a chemoattractant of monocytes, 11 polymorphonuclear leukocyte (PMN) elastase, a marker of neutrophil activation, 12 and MMP activity in PF obtained from 44 patients with angina pectoris (AP) or AMI with or without VSP, who underwent CABG or closure of the VSP. Methods Patients' ProfilesWe enrolled 44 patients with CAD (34 men, 10 women; mean age 67±2 years (mean ± SEM)) who underwent CABG or closure of VSP: 28 had AP (AP group) and the other 16 had AMI (AMI group). In the AMI group, 5 had VSP (VSP group) and the remaining 11 did not (non-VSP AMI group). All AMI patients underwent cardiac surgery within 7 days of the onset of AMI. Diagnosis of AMI was made by typical symptoms, enzyme concentrations and Background In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI a...

The pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.