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Vol. 61. Issue 3.
Pages 327 (March 2008)
Vol. 61. Issue 3.
Pages 327 (March 2008)
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The Kinetics of Metalloproteinase-9: The Significance of the Light-Dark Cycle in Metalloproteinase-9 in Acute Coronary Syndrome
Cinética de la metaloproteasa 9: importancia del ritmo luz-oscuridad de la metaloproteasa 9 en el síndrome coronario agudo
Alberto Domínguez-Rodrígueza, Juan C Kaskib, Pedro Abreu-Gonzálezc, Martín J García-Gonzáleza
a Servicio de Cardiología, Hospital Universitario de Canarias, Tenerife, Spain
b Cardiovascular Biology Research Centre, Division of Cardiac and Vascular Sciences, St. George's University of London, UK
c Departamento de Fisiología, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
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To the Editor:

We have read with great interest the recent article of Rodríguez et al,1 in which the authors provide an excellent review of metalloproteinases (MMP) and atherothrombotic syndromes. However, we would like to make the following comments.

The inflammatory substrate implicated in acute coronary syndrome (ACS) is extremely complex and involves a number of factors related to both activation and modulation.2 MMP-9, in addition to playing a relevant role in the pathophysiology of the atherothrombotic process, may be useful as a biomarker of atherosclerotic risk and a predictor of recurrent coronary artery disease.3 Additionally, it has been observed that MMP-9 concentrations in patients with coronary artery disease are directly associated with inflammatory markers, such as C-reactive protein, interleukin 6, and fibrinogen.4 However, it has also been shown that certain factors, such as age, sex, dyslipidemia, diabetes, hypertension, and smoking, can influence MMP-9 concentrations.3

The scientific literature has described circadian variations in the circulating concentrations of some cytokines and acute phase reactants among patients with ACS.5-7 However, the existence of circadian variations in circulating MMP-9 concentrations has not been observed in healthy volunteers.8 Recent work by our group has shown diurnal variations in MMP-9 serum concentrations among patients with ACS.9 MMP-9 serum values were significantly higher during the light phase (at 9:00 AM) than the dark phase (at 2:00 PM), which indicates that the diurnal variability could, at least partly, have central neuroendocrine regulation, particularly with regard to melatonin, which is a circadian hormone.

MMP studies in patients with ACS offer considerable pathophysiological information regarding destabilization of the atherogenic process. Therefore, an extracellular matrix biomarker should be selected by standardizing the methods of measurement, establishing cutoff points to identify any values that clearly separate populations with different risks, and establishing how often and at what time of the day the blood samples should be drawn.10

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Metaloproteasas, remodelado vascular y síndromes aterotrombóticos..
Rev Esp Cardiol, 60 (2007), pp. 959-67
Tardif JC, Heinonen T, Orloff D, Libby P..
Vascular biomarkers and surrogates in cardiovascular disease..
Circulation, 113 (2006), pp. 2936-42
Jones CB, Sane DC, Herrington DM..
Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome..
Cardiovasc Res, 59 (2003), pp. 812-23
Ferroni P, Basili S, Martini F, Cardarello CM, Ceci F, di Franco M, et al..
Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation..
J Invest Med, 51 (2003), pp. 295-300
Domínguez Rodríguez A, García González MJ, Abreu González P, Ferrer J, Kaski JC..
Relation of nocturnal melatonin levels to C-reactive protein concentration in patients with ST-segment elevation myocardial infarction..
Am J Cardiol, 97 (2006), pp. 10-2
Domínguez Rodríguez A, Abreu González P, García González MJ, Ferrer J, de la Rosa A, Vargas M, et al..
Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction..
Cytokine, 26 (2004), pp. 89-93
Domínguez Rodríguez A, Abreu González P, García MJ, de la Rosa A, Vargas M, Marrero F..
Ritmo luz/oscuridad de las citocinas proinflamatorias en el infarto agudo de miocardio..
Rev Esp Cardiol, 56 (2003), pp. 555-60
Tayebjee MH, Lip GY, Blann AD, MacFadyen RJ..
Effects of age, gender, ethnicity, diurnal variation and exercise on circulating levels of matrix metalloproteinases (MMP)-2 and -9, and their inhibitors, tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2..
Thromb Res, 115 (2005), pp. 205-10
Dominguez Rodriguez A, Abreu Gonzalez P, Garcia Gonzalez MJ, Reiter RJ..
Relation of nocturnal melatonin levels to serum matrix metalloproteinase-9 concentrations in patients with myocardial infarction..
Thromb Res, 120 (2007), pp. 361-6
Kaski JC, Fernández Berges D..
Proteína C reactiva en el servicio de urgencias:¿ha encontrado una aplicación clínica? Rev Esp Cardiol, 60 (2007), pp. 797-800
Revista Española de Cardiología (English Edition)

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