RESEARCH ARTICLE


Matrix Metalloproteinases 2 and 9 are CAD More Relevant Biomarkers Than -1, -8, and -12 to Separate CAD from Non-CAD Patients



Alvaro L. Muller da Fonseca1, 7, 8, Rogério J. B. Oliveira2, Júlio C. A. Santos11, Luciana S. Cardoso3, Fábio D. Couto4, Fernanda W. M. Lima5, Marcelo S. Castilho6, Yehoshua Maor9, Raul D. Santos10, Ricardo D. Couto7, 8, 11, *
1 Laboratory of Immunology, Departamento de Educação (DEDC7), Universidade do Estado da Bahia (UNEB), Rodovia Lomanto Junior, BR 407, Km 127, Senhor do Bonfim, BA, Brazil
2 Naval Hospital of Salvador, Brazilian Marine Forces, Salvador, Bahia, Brazil
3 Laboratory of Parasitology, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, The Federal University of Bahia - UFBA, Salvador, Bahia, Brazil
4 Laboratory of Molecular Biology and Genetics at Center of Agricultural, Environmental and Biological Sciences (CCAAB), The Federal University of the Reconcavo of Bahia – UFRB, Bahia, Brazil
5 Laboratory of Infection Disease Diagnostics - SIDI, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, The Federal University of Bahia - UFBA, Salvador, Bahia, Brazil
6 Laboratory of Bioinformatics and Molecular Modelling Department of Medicines, Faculty of Pharmacy, The Federal University of Bahia - UFBA, Salvador, Bahia, Brazil
7 PGBSMI – Gonçalo Moniz Research Center (CPqGM), Oswaldo Cruz Foundation, Brazilian Ministry of Health (FIOCRUZ), Salvador, Bahia, Brazil
8 Pharmacy Postgraduate Program (PPGFAR), Faculty of Pharmacy, Federal University of Bahia/UFBA, Salvador, Bahia, Brazil
9 Phytor Lab for Drug Development, The Hadassah Medical Center, Hebrew University Jerusalem Biotecnology Park (JBP), Jerusalem,, Israel
10 Lipid Clinic Heart Institute, INCOR, University of São Paulo Medical School Hospital and Preventive Medicine Center and Cardiology Program, Hospital Israelita Albert Einstein, São Paulo, Brazil
11 Clinical Biochemistry Laboratory, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, The Federal University of Bahia - UFBA, Salvador, Bahia, Brazil


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© 2019 Müller da Fonseca et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Clinical Biochemistry Laboratory, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Bahia/UFBA, Salvador, Bahia, Brazil, Rua Barão de Jeremoabo, Nº147, Campus Universitário de Ondina, Ondina, CEP – 40170-115, Salvador, Bahia, Brazil; Tel: + (+5571) 3283-6952/6900; E-mail: rdc@ufba.br


Abstract

Background:

Atherosclerotic Carotid Artery Disease (CAD) is a frequent cause of mortality worldwide. The discovery of biomarkers that evidenced CAD progression would help with cardiovascular risk reduction. Extracellular Matrix Metalloproteinases (MMPs) have been associated with plaque progression, lesion aggravation, and rupture.

Objective:

This study evaluated that MMPs serum optical-densities and digestive gel-activity are associated with CAD.

Methods:

This cross-sectional study evaluated 65 outpatients presenting CAD (n=31) or not (n=34). The Carotid disease was evidenced by Doppler echography. ELISA and SDS-PAGE zymography were performed to determine MMPs serum optical-densities and proteolytic-activity. Principal Component Analysis (PCA) was performed to identify the most relevant MMPs (MMP-1, 2, 8, 9 and 12).

Results:

MMP-2 and MMP-9 showed lower serum optical-densities in CAD (MMP-2, p = 0.0246; and MMP-9, p < 0.0001), but higher digestive enzymatic activity when compared to non-CAD samples (p < 0.0001). PCA analysis strengthens the singling out of those individual MMPs as predictors of choice to differentiate CAD from non-CAD patients as opposed to others MMPs. Analysis of the loadings showed MMP-2 and MMP-9 as the most important independent variables to separate CAD from non-CAD patients.

Conclusion:

MMP-2 and MMP-9 are more relevant biomarkers for CAD than the other MMPs analyzed.

Keywords: Carotid Artery Disease (CAD) biomarkers, Matrix Metalloproteinases (MMPs), Enzymatic activities, Biomarkers of established CAD, Optical-densities, Digestive gel-activity.