To the Editor,
We read with great interest the article by Santos et al1, entitled "Early Change of Extracellular Matrix and Diastolic Parameters in Metabolic Syndrome", which was published in october of Arquivos Brasileiros de Cardiologia. The authors1 aimed to compare diastolic function, biomarkers representing extracellular matrix activity (MMP9 and TIMP1), inflammation and cardiac hemodynamic stress in patients with the metabolic syndrome and healthy controls. We thank authors for their excellent data and valuable study but some comments may be of beneficial.
Matrix metalloproteinases (MMPs) play major roles in tissue development, matrix collagen turnover, repair and remodeling2-5. The TIMPs are usually secreted together with variable amounts of their MMPs and regulate MMPs' proteolytic activities by binding tightly to their catalytic sites2.
Extracellular matrix (ECM) turnover is largely modulated by the interaction between MMPs and their TIMPs.2-5A correlation and reciprocal influences between MMP and their TIMP determines the combined effect on ECM turnover4,5.
Expression patterns of MMP9 andTIMP1 (a specific inhibitor of MMP9), are closely correlated with physiological, pathological and micro-environmental processes characterized by the degradation and accumulation of the ECm3. A balance between MMP9 and TIMP1 is a major parameter in regulating both the enzyme activation and functionality in the tissue3-5. Consequently, MMP9/TIMP1 ratio could be viewed as a more reliable, useful and determinative marker in the evaluation of their potential prognostic capacities compared with MMP9 and TIMP1 separately. Determining the changes in the ECM balance and activity with a more appropriate method could give a chance to observe the influences on the results more precisely.
References
- 1.Santos AB, Junges M, Silvello D, Macari A, Araújo BS, Seligman BG, et al. Early change of extracellular matrix and diastolic parameters in metabolic syndrome. Arq Bras Cardiol. 2013;101(4):311–316. doi: 10.5935/abc.20130182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Roderfeld M, Graf J, Giese B, Salguero-Palacios R, Tschuschner A, Müller-Newen G, et al. Latent MMP-9 is bound to TIMP-1 before secretion. Biol Chem. 2007;388(11):1227–1234. doi: 10.1515/BC.2007.123. [DOI] [PubMed] [Google Scholar]
- 3.Avadanei R, Caruntu ID, Amalinei C, Lozneanu L, Balan R, Grigoras A, et al. High variability in MMP2/TIMP2 and MMP9/TIMP1 expression in secondary liver tumors. Rom J Morphol Embryol. 2013;54(3):479–485. [PubMed] [Google Scholar]
- 4.Cogni AL, Farah E, Minicucci MF, Azevedo PS, Okoshi K, Matsubara BB, et al. Metalloproteinases-2 and -9 predict left ventricular remodeling after myocardial infarction. Arq Bras Cardiol. 2013;100(4):315–321. doi: 10.5935/abc.20130049. [DOI] [PubMed] [Google Scholar]
- 5.Kim Y, Remacle AG, Chernov AV, Liu H, Shubayev I, Lai C, et al. The MMP-9/ TIMP-1 axis controls the status of differentiation and function of myelin-forming Schwann cells in nerve regeneration. PLoS One. 2012;7(3): doi: 10.1371/journal.pone.0033664. [DOI] [PMC free article] [PubMed] [Google Scholar]