Increases in Interleukin-6 and Matrix Metalloproteinase-9 in the Infarct-Related Coronary Artery of Acute Myocardial Infarction

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...

Section: Elevated Proteinase Level As a Marker For Cardiac Tissue Injmentioning

confidence: 99%

Increased Pericardial Fluid Level of Matrix Metalloproteinase-9 Activity in Patients With Acute Myocardial Infarction Possible Role in the Development of Cardiac Rupture

Kameda

Matsunaga

Abe

et al. 2006

“…7,8 Elevated plasma levels of MMP-9 in the peripheral blood have been shown in patients with ACS, 9 and are associated with severe coronary stenosis 10 and cardiovascular mortality. 11 In addition, the plasma MMP-9 level is elevated in the coronary circulation of patients with ACS, 12,13 indicating that the production of MMP-9 may be enhanced in ACS.MMP release, however, may also occur in the interstitium of ischemic myocardium in the early period after a myocardial infarction (MI), 14 as well as from coronary plaque. The serum MMP concentration is associated with left ventricular remodeling after MI, 15 and in particular, an elevated plasma MMP-9 level is associated with infarct size.…”

mentioning

confidence: 99%

Elevation of Plasma Matrix Metalloproteinase-9 in the Culprit Coronary Artery in Patients With Acute Myocardial Infarction Clinical Evidence From Distal Protection

Higo

Uematsu

Yamagishi³

et al. 2005

atrix metalloproteinase (MMP), an extracellular matrix degrading enzyme, plays a crucial role in the breakdown of the fibrous cap of plaque and subsequent rupture in the pathogenesis of acute coronary syndrome (ACS). 1,2 The MMP family has been identified in the shoulder regions of human atherosclerotic plaque, 3 and is more frequently expressed in the coronary plaque of patients with ACS than with stable angina pectoris (SAP). 4 MMP-9 (92-kDa gelatinase) is associated with atherosclerotic arterial remodeling 5 and is actively synthesized in vulnerable plaque. 6 MMP-9 affects plaque stability in association with various inflammatory cytokines. 7,8 Elevated plasma levels of MMP-9 in the peripheral blood have been shown in patients with ACS, 9 and are associated with severe coronary stenosis 10 and cardiovascular mortality. 11 In addition, the plasma MMP-9 level is elevated in the coronary circulation of patients with ACS, 12,13 indicating that the production of MMP-9 may be enhanced in ACS.MMP release, however, may also occur in the interstitium of ischemic myocardium in the early period after a myocardial infarction (MI), 14 as well as from coronary plaque. The serum MMP concentration is associated with left ventricular remodeling after MI, 15 and in particular, an elevated plasma MMP-9 level is associated with infarct size. 16,17 Hence, whether the main source of increased plasma MMP-9 is the culprit coronary plaque or the infarcted myocardium still remains unclear.The aim of this study was to determine the major source of plasma MMP-9 in patients with early phase acute MI (AMI) by measuring the plasma levels of MMP-9 in the coronary artery as well as a peripheral artery of patients with AMI and in those with SAP during percutaneous coronary intervention (PCI) using a distal protection device. We also investigated in situ MMP-9 expression in coronary artery plaque aspirated from patients with AMI and compared it with samples obtained by directional coronary atherectomy (DCA) in patients with SAP. Methods PatientsWe studied 23 consecutive patients with AMI within 24 h from the onset of chest pain (6 women; age range 44-87 years, 64±12 years) and 10 consecutive patients with SAP as the control (5 women; age range 50-71 years, 66±10 years, p=0.61 vs AMI). The diagnosis of AMI was determined on the basis of chest pain lasting longer than 30 min with ST-segment elevation >2 mm in at least 2 Tomoki Ohara, MD; Shinsuke Nanto, MD; Seiki Nagata, MDBackground Although the elevation of circulating plasma matrix metalloproteinase (MMP)-9 levels in patients with acute myocardial infarction (AMI) has been documented, the origin of MMP-9 remains unclear. Methods and ResultsPlasma MMP-9 levels in both the peripheral circulation and coronary arteries were measured in patients with AMI (n=23) and with stable angina pectoris (SAP, n=10) during percutaneous coronary intervention (PCI) with a distal protection device. Blood samples were collected from the femoral artery (FA) and the coronary artery before (Initial) and after (Secon...

“…7 IL-6 could be synthesized by activated macrophages and with vascular smooth muscle cells infiltrating into the atherosclerotic plaque. [12][13][14][15][16] Mechanical stretch, vascular injury and hypoxia may be involved in causing IL-6 release in the coronary circulation after PCI.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6] We demonstrated an increase in regional IL-6 levels in the infarct-related coronary artery in patients with acute myocardial infarction. 7 Recent development of the percutaneous coronary intervention (PCI) technique enables us to rescue patients from acute coronary occlusion. [8][9][10] However, one of the residual problems is restenosis of the coronary artery, which was recanalized by PCI.…”

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confidence: 99%

Close Association of Regional Interleukin-6 Levels in the Infarct-Related Culprit Coronary Artery With Restenosis in Acute Myocardial Infarction

Funayama¹,

Ishikawa²,

Kubo³

et al. 2006

Self Cite

BackgroundThe involvement of interleukin (IL)-6 in restenosis of the recanalized coronary artery after the percutaneous coronary intervention (PCI) was examined. Methods and Results There were 40 patients enrolled in the study who had acute myocardial infarction and whose infarct-related coronary arteries were treated by new thrombectomy devices and stenting. Blood samples were collected from the culprit coronary artery before and immediately after the maneuver of the PCI. Restenosis was defined as residural stenosis because it accounted for more than 50% at the follow-up coronary angiography. Plasma IL-6 levels in the infarct-related coronary artery were 12.8 and 13.2 pg/ml before and after the initial maneuver of the PCI, respectively, values that were significantly greater than that of 7.2 pg/ml in the peripheral vein (p<0.0001). The levels of IL-6 in the pre-and the post-stage of PCI were significantly greater in the patients with restenosis than those without restenosis. The plasma IL-6 levels in the post-stage of PCI had significant correlations with late loss and loss index. Conclusions The present study findings indicate that plasma IL-6 levels in the culprit coronary artery at the post-stage of PCI are closely associated with the future restenosis of the revasculized coronary artery in acute myocardial infarction. (Circ J 2006; 70: 426 -429)