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Plaque Progression (plaque + progression)
Selected AbstractsPlaque progression and regression in atherothrombosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007B. IBANEZ Summary., Atherosclerotic disease is a pathological process characterized by the deposition of lipid and other blood-borne material within the arterial wall. The deposition of these materials and the subsequent thickening of the wall may significantly compromise the vessel lumen. Atherosclerosis is a diffuse disease with focal clinical manifestations that are the consequence of thrombotic complications on disrupted atherosclerotic lesions. Until recently, atherosclerosis development was envisaged as an incessant progressing process; however, new evidence has shown that atherosclerotic plaque homeostasis is not necessarily a constantly progressing process. There are many data showing that atherosclerotic plaque formation can be slowed, stopped or even reversed. Comprehension of the underlying mechanisms involved in the homeostasis of atherosclerotic plaque (progression/regression) should allow the development of interventions enhancing the regression pathway. Novel imaging technology has allowed the accurate evaluation of plaque progression, vital in the assessment of the efficacy of interventions. In this review we discuss the processes involved in the formation and progression of atherosclerotic lesions, the triggers for plaque disruption, as well as new therapies. We also deal with the potential pathways of plaque regression, as well as tools for accurate serial atherosclerotic quantification. [source] TRB3, upregulated by ox-LDL, mediates human monocyte-derived macrophage apoptosisFEBS JOURNAL, Issue 10 2009Yuan-yuan Shang Tribble3 (TRB3), a mammalian homolog of Drosophila tribbles, slows cell-cycle progression, and its expression is increased in response to various stresses. The aim of this study was to investigate the role of the TRB3 gene in macrophage apoptosis induced by oxidized low-density lipoprotein (ox-LDL). We found that, in human monocyte-derived macrophages, TRB3 is upregulated by ox-LDL in a dose- and time-dependent manner. The cell viability of TRB3-overexpressing macrophages was decreased, but apoptosis was increased and the level of activated caspase-3 increased. Factorial analyses revealed no significant interaction between TRB3 overexpression and ox-LDL stimulation with respect to macrophage apoptosis. Furthermore, TRB3-silenced macrophages showed decreased apoptosis, and TRB3-silenced cells treated with ox-LDL showed significantly increased apoptosis. Silencing of TRB3 and ox-LDL stimulation showed significant interaction for macrophage apoptosis, suggesting that TRB3 knockdown resisted the macrophage apoptosis induced by ox-LDL. Therefore, TRB3 in part mediates the macrophage apoptosis induced by ox-LDL, which suggests that TRB3 might be involved in vulnerable atherosclerotic plaque progression. [source] Preventive role of garlic in atherosclerotic plaque progressionFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 1 2000Article first published online: 14 JUN 2010 [source] Activated ,2 macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-,B activation in macrophage-derived cell linesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Leandro C. Cáceres Abstract Macrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-,B signaling pathways. Previously, we demonstrated that activated ,2 -macroglulin (,2M*) through the interaction with its receptor low-density lipoprotein receptor-related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK-ERK1/2. In the present work, we examined whether ,2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that ,2M* promoted MMP-9 expression and protein secretion by LRP1 in both macrophage-derived cell lines, which was mediated by the activation of MAPK-ERK1/2 and NF-,B. Both intracellular signaling pathways activated by ,2M* were effectively blocked by calphostin-C, suggesting involvement of PKC. In addition, we demonstrate that ,2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the ,2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1, and NF-,B, it was shown that the ,2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the ,2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression. J. Cell. Biochem. 111: 607,617, 2010. © 2010 Wiley-Liss, Inc. [source] Vulnerable Plaque: The Pathology of Unstable Coronary LesionsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 6 2002RENU VIRMANI M.D. Vulnerable plagues have been defined as precursors to lesions that rupture. However, coronary thrombosis may occur from other lesions like plaque erosion and calcified nodules, although to a lesser frequency than rupture. Therefore, the definition of vulnerable plaque should be all-inclusive. Using descriptive terminology, the authors define the precursor lesion of plaque rupture as "thin-cap fibroatheroma" (TCFA). Morphologically, TCFAs have a necrotic core with an overlying thin fibrous cap (< 65 mm) consisting of collagen type I, which is infiltrated by macrophages. These lesions are most frequent in the coronary tree of patients dying with acme myocardial infarction and least common in those with plaque erosion. TCFAs are more common in patients with high serum total cholesterol (TC) and a high TC to high density cholesterol ratio, in women >50 years, and in those patients with elevated levels of high sensitivity C-reactive protein. TCFAs are mostly found in the proximal left anterior descending coronary arteries and less commonly in the proximal right or the proximal left circumflex coronary arteries. In TCFAs, necrotic core length is , 2,17 mm (mean 8 mm) and the underlying cross-sectional luminal narrowing in over 75% of cases is < 75% (< 50% diameter stenosis). The area of the necrotic core in at least 75% of cases is ,3 mm2. Clinical studies of TCFAs are limited as angiography and intravascular ultrasound (TVUS) catheters cannot precisely identify these lesions. Newer catheters and other techniques are at various stages of development and will play a significant role in the understanding of plaque progression and the development of symptomatic coronary artery disease. [source] Imaging biomarkers of cardiovascular diseaseJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2010Jinnan Wang PhD Abstract Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Current clinical techniques that rely on stenosis measurement alone appear to be insufficient for risk prediction in atherosclerosis patients. Many novel imaging methods have been developed to study atherosclerosis progression and to identify new features that can predict future clinical risk. MRI of atherosclerotic vessel walls is one such method. It has the ability to noninvasively evaluate multiple biomarkers of the disease such as luminal stenosis, plaque burden, tissue composition and plaque activity. In addition, the accuracy of in vivo MRI has been validated against histology with high reproducibility, thus paving the way for application to epidemiological studies of disease pathogenesis and, by serial MRI, in monitoring the efficacy of therapeutic intervention. In this review, we describe the various MR techniques used to evaluate aspects of plaque progression, discuss imaging-based measurements (imaging biomarkers), and also detail their validation. The application of plaque MRI in clinical trials as well as emerging imaging techniques used to evaluate plaque compositional features and biological activities are also discussed. J. Magn. Reson. Imaging 2010;32:502,515. © 2010 Wiley-Liss, Inc. [source] Reproducibility of black blood dynamic contrast-enhanced magnetic resonance imaging in aortic plaques of atherosclerotic rabbitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2010Claudia Calcagno MD Abstract Purpose: To investigate the short-term reproducibility of black-blood dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in atherosclerotic rabbits to evaluate the potential of this technique to be a reliable readout of plaque progression and/or regression upon therapeutic intervention. Materials and Methods: Atherosclerotic rabbits were imaged at baseline and 24 hours later with DCE-MRI on a 1.5T MRI system. DCE-MRI images were analyzed by calculating the area under the signal intensity versus time curve (AUC). Intraclass correlation coefficients (ICCs) were used to evaluate interscan, intraobserver, and interobserver reproducibility. In addition, the test,retest coefficient of variation (CoV) was evaluated. Results: Statistical analyses showed excellent interscan, intraobserver, and interobserver agreement. All ICCs were greater than 0.75, P < 0.01 indicating excellent agreement between measurements. Conclusion: Experimental results show good interscan and excellent intra- and interobserver reproducibility, suggesting that DCE-MRI could be used in preclinical settings as a read-out for novel therapeutic interventions for atherosclerosis. This preliminary work encourages investigating the reproducibility of DCE-MRI also in clinical settings, where it could be used for monitoring high-risk patients and in longitudinal clinical drug trials. J. Magn. Reson. Imaging 2010;32:191,198. © 2010 Wiley-Liss, Inc. [source] Plaque progression and regression in atherothrombosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007B. IBANEZ Summary., Atherosclerotic disease is a pathological process characterized by the deposition of lipid and other blood-borne material within the arterial wall. The deposition of these materials and the subsequent thickening of the wall may significantly compromise the vessel lumen. Atherosclerosis is a diffuse disease with focal clinical manifestations that are the consequence of thrombotic complications on disrupted atherosclerotic lesions. Until recently, atherosclerosis development was envisaged as an incessant progressing process; however, new evidence has shown that atherosclerotic plaque homeostasis is not necessarily a constantly progressing process. There are many data showing that atherosclerotic plaque formation can be slowed, stopped or even reversed. Comprehension of the underlying mechanisms involved in the homeostasis of atherosclerotic plaque (progression/regression) should allow the development of interventions enhancing the regression pathway. Novel imaging technology has allowed the accurate evaluation of plaque progression, vital in the assessment of the efficacy of interventions. In this review we discuss the processes involved in the formation and progression of atherosclerotic lesions, the triggers for plaque disruption, as well as new therapies. We also deal with the potential pathways of plaque regression, as well as tools for accurate serial atherosclerotic quantification. [source] Serum interleukin-6 is elevated in symptomatic carotid bifurcation diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009M. Koutouzis Introduction,,, The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. Methods,,, One hundred nineteen patients (91 men and 28 women; mean age 66 ± 8 years; range 42,83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-, (TNF-,), IL-1,, serum amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. Results,,, Serum IL-6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0,6.5] pg/ml vs 2.5 [1.9,4.1] pg/ml, P = 0.02). TNF-,, IL-1,, SAA, and hs-CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 ± 0.1% vs 0.4 ± 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. Conclusion,,, Patients with symptomatic carotid atherosclerotic disease have elevated serum IL-6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque. [source] | ||||||||||