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Extracelluar Matrix Metalloproteinase Inducer (EMMPRIN), Acute Myocardial Infarction and the Kounis Syndrome
Archives of Medical Research 41 (2010) 150
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Extracelluar Matrix Metalloproteinase Inducer (EMMPRIN), Acute Myocardial Infarction and the Kounis Syndrome Matrix metalloproteinases (MMPs) play an important role in ventricular remodeling after acute myocardial infarction (AMI). How to control the expression of MMPs is still a problem. Recent studies show the extracellular MMP inducer (EMMPRIN) is expressed on the cardiac myocytes and can induce MMP expression (1). In our investigation, we found that EMMPRIN expression increased in the human left ventricle and is correlated with MMP-2 and MMP-9 expression after AMI. This study underscores the potential of EMMPRIN as a novel target for AMI ventricular remodeling (2). We thank Kounis and colleagues for their interest in our manuscript. In their letter to the journal, they raised an important discussion point concerning our recent publication. In their point, mast cells play a critical role in vulnerability of atheromatous plaques. Many studies show that accumulation of activated mast cells was found at the site of atheromatous erosion or rupture in recent acute myocardial infarction and play a critical role in Kounis syndrome type II variant patients (3). Recent studies also show that EMMPRIN was expressed in atherosclerotic plaque and may cause plaque instability (4). So the relationship between activated mast cells and EMMPRIN expression in plaque rupture should be concerned. We would like to underline that our study mainly focused on the expression of MMPs and EMMPRIN in the area surrounding the infarct zone. In our study we also found that a massive influx of inflammatory cells was also observed in the ruptured infarcts. In the acute phase, neutrophils are major participants in myocardial ischemia and reperfusion (5,6). In later stages, macrophages and mast cells provide amounts of cytokines and growth factors mediating myocardial repair, and many evidences support that mast cells participate mainly in fibrotic processes (7). As our reader points out that activated mast cells can release their neutral proteases and then activate the MMPs such as MMP-2 and MMP-9. In the Kounis syndrome, activated mast cells released the inflammatory mediators, which would stimulate macrophages and T-lymphocytes. Many studies have demonstrated that inflammatory mediators can stimulate EMMPRIN expression of inflammatory cells (including mast cells) and vice versa. At this point, mast cells activate MMP-2 and MMP-9, also possibly by
EMMPRIN. Numerous experimental studies report that the use of specific anti-inflammatory strategies can reduce infarct size and improve ventricular remodeling; however, up to now all attempts to relieve inflammatory injury in clinical practice have been unsuccessful. Therefore, inhibition of EMMPRIN expression could be a promising approach for the prevention or treatment of ventricular remodeling in AMI subjects. Although it is difficult to clarify the role of mast cells in ventricular remodeling, it is really an important issue that warrants further investigation. References 1. Spinale FG, Coker ML, Heung LJ, et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation 2000;102:1944e1949. 2. Nie R, Xie S, Du B, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) is increased in human left ventricle after acute myocardial infarction. Arch Med Res 2009;40:605e611. 3. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7e14. 4. Xie S, Nie R, Wang J. Inhibiting extracellular matrix metalloproteinase inducer maybe beneficial for diminishing the atherosclerotic plaque instability. J Postgrad Med 2009;55:284e286. 5. Hansen PR. Role of neutrophils in myocardial ischemia and reperfusion. Circulation 1995;91:1872e1885. 6. Cleutjens JP, Blankesteijn WM, Daemen MJ, et al. The infarcted myocardium: simply dead tissue, or a lively target for therapeutic interventions. Cardiovasc Res 1999;44:232e241. 7. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77: 1033e1079.
0188-4409/$esee front matter. Copyright Ó 2010 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2010.02.008
SHUANGLUN XIE RUQIONG NIE and JINGFENG WANG Department of Cardiology The Second Affiliated Hospital of Sun Yat-sen University Guangzhou, 510120, China Address reprint requests to: Jingfeng Wang, M.D. Department of Cardiology The Second Affiliated Hospital of Sun Yat-sen University Yanjiang Road 107 Guangzhou, 510120, China Phone: (þ86 020) 81332623 Fax: (þ86 020) 81332623 E-mail: [email protected]
REPLY
Extracelluar Matrix Metalloproteinase Inducer (EMMPRIN), Acute Myocardial Infarction and the Kounis Syndrome Matrix metalloproteinases (MMPs) play an important role in ventricular remodeling after acute myocardial infarction (AMI). How to control the expression of MMPs is still a problem. Recent studies show the extracellular MMP inducer (EMMPRIN) is expressed on the cardiac myocytes and can induce MMP expression (1). In our investigation, we found that EMMPRIN expression increased in the human left ventricle and is correlated with MMP-2 and MMP-9 expression after AMI. This study underscores the potential of EMMPRIN as a novel target for AMI ventricular remodeling (2). We thank Kounis and colleagues for their interest in our manuscript. In their letter to the journal, they raised an important discussion point concerning our recent publication. In their point, mast cells play a critical role in vulnerability of atheromatous plaques. Many studies show that accumulation of activated mast cells was found at the site of atheromatous erosion or rupture in recent acute myocardial infarction and play a critical role in Kounis syndrome type II variant patients (3). Recent studies also show that EMMPRIN was expressed in atherosclerotic plaque and may cause plaque instability (4). So the relationship between activated mast cells and EMMPRIN expression in plaque rupture should be concerned. We would like to underline that our study mainly focused on the expression of MMPs and EMMPRIN in the area surrounding the infarct zone. In our study we also found that a massive influx of inflammatory cells was also observed in the ruptured infarcts. In the acute phase, neutrophils are major participants in myocardial ischemia and reperfusion (5,6). In later stages, macrophages and mast cells provide amounts of cytokines and growth factors mediating myocardial repair, and many evidences support that mast cells participate mainly in fibrotic processes (7). As our reader points out that activated mast cells can release their neutral proteases and then activate the MMPs such as MMP-2 and MMP-9. In the Kounis syndrome, activated mast cells released the inflammatory mediators, which would stimulate macrophages and T-lymphocytes. Many studies have demonstrated that inflammatory mediators can stimulate EMMPRIN expression of inflammatory cells (including mast cells) and vice versa. At this point, mast cells activate MMP-2 and MMP-9, also possibly by
EMMPRIN. Numerous experimental studies report that the use of specific anti-inflammatory strategies can reduce infarct size and improve ventricular remodeling; however, up to now all attempts to relieve inflammatory injury in clinical practice have been unsuccessful. Therefore, inhibition of EMMPRIN expression could be a promising approach for the prevention or treatment of ventricular remodeling in AMI subjects. Although it is difficult to clarify the role of mast cells in ventricular remodeling, it is really an important issue that warrants further investigation. References 1. Spinale FG, Coker ML, Heung LJ, et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation 2000;102:1944e1949. 2. Nie R, Xie S, Du B, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) is increased in human left ventricle after acute myocardial infarction. Arch Med Res 2009;40:605e611. 3. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7e14. 4. Xie S, Nie R, Wang J. Inhibiting extracellular matrix metalloproteinase inducer maybe beneficial for diminishing the atherosclerotic plaque instability. J Postgrad Med 2009;55:284e286. 5. Hansen PR. Role of neutrophils in myocardial ischemia and reperfusion. Circulation 1995;91:1872e1885. 6. Cleutjens JP, Blankesteijn WM, Daemen MJ, et al. The infarcted myocardium: simply dead tissue, or a lively target for therapeutic interventions. Cardiovasc Res 1999;44:232e241. 7. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77: 1033e1079.
0188-4409/$esee front matter. Copyright Ó 2010 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2010.02.008
SHUANGLUN XIE RUQIONG NIE and JINGFENG WANG Department of Cardiology The Second Affiliated Hospital of Sun Yat-sen University Guangzhou, 510120, China Address reprint requests to: Jingfeng Wang, M.D. Department of Cardiology The Second Affiliated Hospital of Sun Yat-sen University Yanjiang Road 107 Guangzhou, 510120, China Phone: (þ86 020) 81332623 Fax: (þ86 020) 81332623 E-mail: [email protected]