Editorial, Int J Cardiovasc Res Vol: 1 Issue: 2
Carotid Plaque and MMP-9 Controversies
|Liz Andrea Villela Baroncini*
|Pontifical Catholic University of Parana, Brazil
|Corresponding author : Liz Andrea Villela Baroncini
Pontifical Catholic University of Parana, Brazil
|Received: June 19, 2012 Accepted: June 22, 2012 Published: June 25, 2012
|Citation: Villela Baroncini (2012) Carotid Plaque and MMP-9 Controversies. Int J Cardiovasc Res 1:2 doi:10.4172/2324-8602.1000e107
Carotid Plaque and MMP-9 Controversies
Advanced carotid plaques are complex structures that are in constantly remodeling process which complicates their histological characterization and classification. The natural history of the plaque progression and destabilization does not occur in a linear manner. At the present, is not possible to predict whether a carotid plaque will become symptomatic or when symptoms will occur.Patients may exhibit the same carotid plaque histological components whether they are symptomatic or asymptomatic.
|Advanced carotid plaques are complex structures that are in constantly remodeling process which complicates their histological characterization and classification. The natural history of the plaque progression and destabilization does not occur in a linear manner. At the present, is not possible to predict whether a carotid plaque will become symptomatic or when symptoms will occur. Patients may exhibit the same carotid plaque histological components whether they are symptomatic or asymptomatic. Fibrotic and calcific plaques could become vulnerable, where as complex plaques with surface defects, hemorrhage, and thrombus could remain silent. Lesions considered advanced by their histology may or may not narrow the arterial lumen, may or may not be visible by angiography, and may or may not produce clinical manifestations. The American Heart Association classification of human atherosclerotic lesions considers the presence or absence of different tissue components in plaques, but does not account for the proportion of each component or its location in the plaque. Because plaques are dynamic structures, changing through process of stabilization and destabilization, the locations and the proportions of different plaque components are constantly being modified. Therefore, the presence or absence of patients’ symptoms determines the classification of the plaques in stable or vulnerable in clinical daily practice. In some histological analysis, used to classify the plaque, specific regions within the plaque (e.g., the plaque shoulder) are assessed. However, several reports suggest that vulnerability to plaque rupture is a multifocal phenomenon, particularly at the time of acute presentation. Also, the imbalanced degradation and synthesis of the extracellular matrix persists in advanced lesions, particularly in plaques with acute disruption. The vulnerability of the atherosclerotic plaques depends on many factors, including endothelial function, presence of inflammatory cells, cytokine production, smooth muscle cells contents, and cell death (including necrosis and apoptosis).
|Carotid atherosclerotic plaque remodeling and an increased risk of symptomatic plaque seem to be partially mediated by matrix metalloproteinases (MMPs). MMPs are around 20 or more zinc containing endopeptidades involved in the metabolism of extracellular matrix as well as the breakdown of other proteins. MMPs have activity against most of the extracellular matrix macromolecules. Its members are partly categorized into groups according to their structure or preferred substrates such as collagenases, gelatinases, stromelysins, matrilysins, and MMP membrane ligands that are involved in the degradation and remodeling of extracellular matrix. These activities have been implicated in several normal and pathological processes such as progression and formation of atherosclerotic lesion, destabilization, and plaque rupture and also in the stabilization and cicatrization of the plaque. Overexpression of active MMP contributes to the dissolution of the collagenous matrix in the fibrous cap, causing structure to weaken and become brittle and more susceptible to rupture when exposed to hemodynamic stress. The expression of 72-kDA (MMP-2) and 92 kDA (MMP-9) gelatinase has been demonstrated within human atherosclerotic lesions and is implicated in plaque rupture, and, consequently, in acute ischemic events. However, previous reports have failed to detect a positive correlation between MMP-9 and symptomatic plaques. Instead, the level of MMP-9 appears to be related to the age of the patient and the quantity of fibrous tissue in the plaque. The mechanisms linking MMP-9 expression within plaques and atherosclerosis still are speculative and maybe explained as an epiphenomenon of the increased number of macrophages within the vulnerable plaque. However, plaques from MMP-9 knockout mice are associated with a lower macrophage content compared with those of wild type mice, suggesting a primary role of MMP-9 in macrophage migration and activity.
|The finding of high concentrations of MMP-9 in normal arterial tissue as well in atherosclerotic carotid plaques from asymptomatic and asymptomatic patients confirms the great discussion in the existing literature on the actual role of these proteins in the processes of stabilization/destabilization of the plaque. MMP-9 is present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. It is part of the atherogenesis process and is not specifically a factor in acute disruption event. MMP-9 are produced by both macrophages and smooth muscle cells and thus it is expected to act in both these acute ischemic events where there is an extensive infiltration of macrophages and in part of stable plaque acting at continuous remodeling of extracellular matrix.
|Finally, the literature is controversial on protein expression, especially regarding the metalloproteinases and macrophages, which opens the planning of new studies with different techniques.