American Journal of Emergency Medicine (2012) 30, 1210-1211

Editorial

From molecular cardiology to emergency medical practice: the role of inflammatory markers

Joyce Vazquez^{a, b}, Joseph Varon MD^{c, d, e,}?

^aDorrington Medical Associates, PA, Houston, TX 77030, USA

^bUniversidad Anahuac Mexico Norte, Mexico City 52786, Mexico

^cChief of Critical Care Services, University General Hospital, Houston, TX 77054, USA

^dClinical Professor of Medicine and Professor of Acute and Continuing Care, The University of Texas Health Science Center at Houston, TX 77030-3209, USA

^eClinical Professor of Medicine, The University of Texas Medical Branch at Galveston, Houston, TX 77555, USA

Received 26 July 2011; accepted 26 July 2011

Matrix metalloproteinases (MMPs) are best known as proteases responsible for the degradation and remodeling of extracellular matrix proteins [1]. Among the membrane- type MMPs, MMP14 and MMP16 degrade native collagen. The collagen breakdown products are substrates for additional gelatinases (MMP2, MMP9). From a pathophys- iological standpoint, MMP activation is achieved by cleavage of a pro-MMP form and is regulated by several cytokines and growth factors. The MMP activators include urokinase plasminogen activator, matrix metalloprotei- nases, interleukin-1, interleukin-6, tumor necrosis factor-?, epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, and cluster of differentiation 40.9, whereas tumor necrosis factor-b, heparin, steroids, and tissue inhibitor of metalloproteinases (TIMP-1 to -4) inhibit MMP activity [2,3].

This extracellular matrix biology has expanded the field of molecular medicine and has significant repercussions in the fields of emergency and critical care. Many Emergency practitioners are not aware that MMPs are important regulatory molecules in both physiological and pathological

* Corresponding author. Tel.: +1 713 669 1670; fax: +1 713 669 1671.

E-mail address: [email protected] (J. Varon).

conditions, including inflammation, cancer, and various acute cardiovascular pathologies [4]. Because of their ability to degrade extracellular matrix components, it is important that the activity of these enzymes is kept under tight control [2,5]. Recent data suggest that the use of selective pharmacological inhibitors might lead to new therapies and represent a useful strategy for the prevention for acute and chronic inflammatory vascular diseases [1,3,4,6].

In this issue of The American Journal of Emergency Medicine, Zhong and associates [7] present an elegant basic science assessment of the imbalance that occurs between MMP-9 and TIMP-1 in the setting of ventricular fibrillation (VF) after the return of spontaneous circulation. In this study, the levels of MMP-9 were higher in VF, particularly in the group with longer-duration VF. In addition, a negative correlation was found between TIMP-1 and the left atrium dimension and left ventricular diastolic dimension. There was a positive correlation between TIMP-1 and the left ventricular ejection fraction.

The results of this study are quite interesting and partially explain the postresuscitation cardiac dysfunction syndrome. Evaluating the impact of functional variations after a successful cardiopulmonary resuscitation can lead in the foreseeable future to having an opportunity for long- term outcomes and prognosis. As emergency practitioners,

0735-6757/$ - see front matter (C) 2012 doi:10.1016/j.ajem.2011.07.020

Editorial

integrating this basic science research and understanding the mechanistic relationship with respect to myocardial

References

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MMP expression and the left ventricular remodeling process can have a profound effect on our daily practice [8]. For example, in other clinical arenas, specific patterns of cytokine and matrix metalloproteinase release may be used as biomarkers for predicting and managing the postoperative course after surgery for congenital heart disease [9]. These complex molecular structures retard the development of heart failure after myocardial infarction, and they have been shown to improve the fractional shortening and smaller increase in end-systolic and end- diastolic dimensions of the infarcted heart [8,10]. From a predictive standpoint, some studies have shown that plasma MMP-9 concentration was a predictor of cardiovascular mortality [11]. Commercially available assays are being developed for this purpose and likely to be used in the emergency department in the near future.

Why are articles like the one by Zhong and colleagues important in the field of emergency medicine? Emergency practitioners need to understand this basic scientific background as an essential component in medical practice. In this particular area, the design of specific inhibitors for these metalloproteinases is an important future challenge. Such inhibitors will be useful not only for gaining insights into the biological roles of MMPs but also for the development of therapeutic interventions for diseases associated with an unbalanced extracellular matrix degrada- tion. Clearly, several inflammatory markers are emerging as potential clinical tools that may provide a therapeutic approach to slow down the time course of the development of heart failure and dysfunction in selected circumstances, such as the postresuscitation period.

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