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

Abstract

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...

Relationships of adiponectin and matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio with coronary plaque morphology in patients with acute coronary syndrome

“…Previous studies (13)(14)(15)(16) have suggested that adiponectin has anti-inflammatory properties and that it may regulate inflammatory responses at atherosclerotic lesions, in which MMPs and TIMPs are abundantly present. Thus, the present study was designed to elucidate the effects of adiponectin and the MMP-9/TIMP-1 ratio on the stability of plaques in ACS and the relationship between them.…”

“…The MMP family has been identified in the shoulder regions of human atherosclerotic plaque (13) and is more frequently expressed in the coronary plaque of patients with ACS than with stable angina pectoris (14). TIMP-1 is also involved in plaque formation (15), and MMP-9 is mainly released into the coronary circulation from the culprit coronary artery plaque in patients with acute myocardial infarction (AMI) (16).…”

High Incidence of Actinobacillus Actinomycetemcomitans Infection in Acute Coronary Syndrome

“…35) RANKL from T-cells stimulates vascular smooth muscle cells (VSMC) to produce matrix metalloproteinase-9 (MMP-9), which destabilizes atherosclerotic plaques 36) and recently was reported to be elevated in coronary artery plaque in patients with acute myocardial infarction. 37) It is less clear why A. actinomycetemcomitans could not be detected in chronic CHD while there was no change in periodontal status. An elevated antibody response to A. actinomycetemcomitans has been reported to function to eliminate the bacteria.…”

RECS1 is a Negative Regulator of Matrix Metalloproteinase-9 Production and Aged RECS1 Knockout Mice are Prone to Aortic Dilation

“…As gelatinases contribute to CMD and aortic aneurysms, [1][2][3][4][5][6]14 we examined their levels in the descending thoracic aortas of young (3 months) and old (16-17 months) WT and KO mice (referred to as YWT, YKO, OWT, and OKO) by gelatin zymography and Western blot analysis (Figs 2A-C). Two main observations were made about aortic MMP-9 levels.…”