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.
Highlights
Atherosclerosis is a multifactorial disease with outcomes that can be identified by measurement of markers such as plaque presence or extension, modifications in vascular wall components, blood hemodynamics, vessel lumen stenosis, and inflammatory markers
Matrix Metalloproteinases (MMPs)-2 and MMP-9 showed lower serum optical-densities in Carotid Artery Disease (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)
In order to understand the underlying reason for this separation, the loading plot was inspected: MMP-1 and MMP-12 have a high load on PC1 (≥0.80), whereas MMP-2 and MMP-9 contribute mainly to PC2 (≥0.80)
Summary
Atherosclerosis is a multifactorial disease with outcomes that can be identified by measurement of markers such as plaque presence or extension, modifications in vascular wall components, blood hemodynamics, vessel lumen stenosis, and inflammatory markers. Atherosclerotic Carotid Artery Disease (CAD) is a frequent cause of morbidity and mortality worldwide. The identification of biomarkers that contribute to CAD would help to improve risk stratification and to implement novel preventive therapies, in addition to classical ones like lipid-lowering and anti-thrombus formation. The latter two despite their effectiveness, do not abrogate the risk of cardiovascular events [1, 2]. Immune and inflammatory pathophysiological processes have gained remarkable interest in the last decades due to association with CAD development, because those processes can generate specific serum measurable biomarkers [2 - 5], such as Metalloproteases (MMP), that are commonly related to vascular wall remodeling [6, 7]. Extracellular Matrix Metalloproteinases (MMPs) have been associated with plaque progression, lesion aggravation, and rupture
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