Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis

Alvarez, Bruna; Ruiz, C. J. Gómez; Chacón, Pilar; Alvarez-Sabin, José; Matas, M.

doi:10.1016/j.jvs.2004.06.023

Cited by 100 publications

(73 citation statements)

References 19 publications

(24 reference statements)

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“…98,99 Macrophage activity quantified by PET 100 and neovascular angiogenesis assessed by MRI have been observed in experimental models. 101 Biomarkers such as C-reactive protein and certain matrix metalloproteinases with the potential to identify carotid plaque instability have also been investigated, [102][103][104] but the reliability of biomarkers in predicting clinical events has not been established. Several studies have shown that plaque composition is modified by treatment with statins.…”

Section: Characterization Of Atherosclerotic Lesions In the Extracranmentioning

confidence: 99%

2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease

Brott¹,

Halperin²,

Abbara

et al. 2011

Stroke

139

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Section: Characterization Of Atherosclerotic Lesions In the Extracranmentioning

confidence: 99%

2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease

Brott¹,

Halperin²,

Abbara

et al. 2011

Stroke

139

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“…A significant increase in MMP-9 immunopositivity has also been demonstrated in atherosclerotic lesions of the aorta and carotid artery of rabbits fed a high-cholesterol diet [161]. Increased plasma levels of circulating MMP-9, as well as MMP-2, also correlate with the clinical symptoms of plaque instability and rupture in the coronary and cerebral circulation [162,163] as well as being found in patients affected by myocardial infarction [164,165], suggesting that MMP-9 may be useful as a biomarker for acute coronary syndrome [166,167].…”

Section: Introductionmentioning

confidence: 96%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…1 Elevated serum MMP-9 concentration is associated with carotid plaque instability and the presence of infiltrated macrophages. 2 Furthermore, analysis of the presence of MMP-9 protein by ELISA within excised carotid plaques revealed high MMP-9 protein mass in calcified segments at or near the carotid bifurcation and in segments with intraplaque hemorrhage. Gelatin zymography showed an increased gelatinase activity of MMP-9 in these segments.…”

mentioning

confidence: 99%

Multispectral Near-Infrared Fluorescence Molecular Imaging of Matrix Metalloproteinases in a Human Carotid Plaque Using a Matrix-Degrading Metalloproteinase–Sensitive Activatable Fluorescent Probe

et al. 2009

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F ormation of unstable atherosclerotic plaque in the internal carotid artery carries a high risk for emboli and subsequent cerebral ischemic events. The fibrous cap of such a plaque may become thin and rupture as a result of the depletion of matrix components through the activation of proteolytic enzymes such as matrix-degrading proteinases. Enhanced matrix breakdown has been attributed primarily to a family of matrix-degrading metalloproteinases (MMPs) that are highly concentrated in atherosclerotic plaques by inflammatory cells (eg, macrophages, foam cells), smooth muscle cells and endothelial cells. 1 Elevated serum MMP-9 concentration is associated with carotid plaque instability and the presence of infiltrated macrophages. 2 Furthermore, analysis of the presence of MMP-9 protein by ELISA within excised carotid plaques revealed high MMP-9 protein mass in calcified segments at or near the carotid bifurcation and in segments with intraplaque hemorrhage. Gelatin zymography showed an increased gelatinase activity of MMP-9 in these segments. 3 These data favor the important role of MMP-9 in the pathogenesis of plaque instability. We analyzed the topographic distribution of MMPs within an excised human carotid plaque by applying multispectral near-infrared fluorescence (NIRF) imaging (IVIS Spectrum, Caliper Life Sciences, Hopkinton, Mass).A surgical endarterectomy was performed on a 74-year-old women with a left-sided, symptomatic, Ͼ70% carotid stenosis. Immediately after endarterectomy, the plaque was placed in PBS and transported to the NIRF system. The plaque was then stretched out and fixed on a silicon plate with 25G needles. A PBS NIRF image was generated from both the intraluminal and extraluminal side of the plaque to determine the level of autofluorescence (background) (Figure 1). After (Figure 1). Compared with the autofluorescence signal obtained without incubation with MMPSense, a 6-and 7-fold increase of the total NIRF signal was observed on the intraluminal and extraluminal side, respectively, after incubation with MMPSense 680. The NIRF signal was not homogeneously distributed across the plaque surface but rather resulted in the identification of areas with high NIRF intensity (denominated as "hot spots") and areas with relatively low NIRF intensity (so-called "cold spots") ( Figure 1). Because MMP-9 activity has been positively correlated with plaque instability as described above, we next determined the contribution of MMP-9 to the NIRF signals as shown in Figure 1. To this end, in situ zymography was performed on tissue sections from excised hot and cold spots as indicated in Figure 1 by the framed areas. After we had used dye-quenched gelatin as Figure 2. Hot spot identified using NIRF is characterized by increased gelatinase activity compared with coldspot. In situ zymography was performed on cryosections (7 m) of cold (A) and hot spot (B). To this end, sections were incubated with DQ-gelatin (50 g/mL, EnzCheck Gelatinase/Collagenase Assay Kit, Invitrogen-Molecular Probes, Breda, the Netherla...

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Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis

Cited by 100 publications

References 19 publications

2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease

2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Multispectral Near-Infrared Fluorescence Molecular Imaging of Matrix Metalloproteinases in a Human Carotid Plaque Using a Matrix-Degrading Metalloproteinase–Sensitive Activatable Fluorescent Probe

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