Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms

Fiotti, Nicola; Moretti, Michèle; Bussani, Rossana; Altamura, Nicola; Zamolo, Francesca; Gerloni, Riccardo; Ukovich, Laura; Ober, Elisa; Silvestri, Furio; Grassi, Gabriele; Adovasio, R; Giansante, Carlo

doi:10.1016/j.atherosclerosis.2010.12.010

Cited by 20 publications

(15 citation statements)

References 30 publications

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“…Moreover, the total MMP/TIMP ratio exhibited a further favorable shift in the combined treatment group compared to each of the monotherapies. MMP-8 and MMP-9 constitute emerging and well-documented, mediators of atherosclerotic plaque stability [39], [40]. The MMPs inhibitor, TIMP-1, has been documented to contribute to atherosclerotic plaque stability [41].…”

Section: Discussionmentioning

confidence: 99%

The Complementary Effects of Atorvastatin and Exercise Treatment on the Composition and Stability of the Atherosclerotic Plaques in ApoE Knockout Mice

et al. 2014

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AimThis study aimed to investigate the effects of combined atorvastatin and exercise treatment on the composition and stability of the atherosclerotic plaques in apolipoproteinE (apoE) knockout mice.MethodsForty male, apoE−/− mice were fed a high-fat diet for 16 weeks. Thereafter, while maintained on high-fat diet, they were randomized into four (n = 10) groups for 8 additional weeks: Group CO: Control. Group AT: Atorvastatin treatment (10 mg/Kg/day). Group EX: Exercise-training on treadmill. Group AT+EX: Atorvastatin and simultaneous exercise training. At the study’s end, plasma cholesterol levels, lipids and triglycerides were measured, along with the circulating concentrations of matrix-metalloproteinases (MMP-2,3,8,9) and their inhibitors (TIMP-1,2,3). Plaque area and the relative concentrations of collagen, elastin, macrophages, smooth muscle cells, MMP-2,3,8,9 and TIMP-1,2,3 within plaques were determined. Lastly, MMP activity was assessed in the aortic arch.ResultsAll intervention groups showed a lower degree of lumen stenosis, with atheromatous plaques containing more collagen and elastin. AT+EX group had less stenosis and more elastin compared to single intervention groups. MMP-3,-8 -9 and macrophage intra-plaque levels were reduced in all intervention groups. EX group had increased TIMP-1 levels within the lesions, while TIMP-2 was decreased in all intervention groups. The blood levels of the above molecules increased during atherosclerosis development, but they did not change after the therapeutic interventions in accordance to their intra-plaque levels.ConclusionThe two therapeutic strategies act with synergy regarding the extent of the lesions and lumen stenosis. They stabilize the plaque, increasing its content in elastin and collagen, by influencing the MMP/TIMP equilibrium, which is mainly associated with the macrophage amount. While the increased MMP-2,-3,-8 -9, as well as TIMP-1 and TIMP-2 circulating levels are markers of atherosclerosis, they are not correlated with their corresponding concentrations within the lesions after the therapeutic interventions, and cannot serve as markers for the disease development/amelioration.

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Section: Discussionmentioning

confidence: 99%

The Complementary Effects of Atorvastatin and Exercise Treatment on the Composition and Stability of the Atherosclerotic Plaques in ApoE Knockout Mice

et al. 2014

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“…In line with our results, a report carried out on hemodialysis patients showed that the genotype GG/GG of MMP-1 G-1607GG in combination with the 6A/6A of MMP-3 significantly increased the mortality risk in these patients [20]. However, these findings seem to conflict with a very recent report, which had demonstrated that carriers of MMP-1 GG show smaller and more stable plaques as well as better prognosis in patients with unstable angina and non-ST elevation myocardial infarction [21]. This controversy may be explained by many factors.…”

Section: Discussionmentioning

confidence: 78%

“…As, in our study, patients were followed prospectively for a long period (median = 2.5 years). However, Fiotti et al [21] considered in hospital follow-up. Third, contradictory results found in many studies, which investigate the association between the GG allele of MMP-1G-1607GG and the risk of artery diseases may also result in this controversy.…”

Section: Discussionmentioning

confidence: 98%

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the outcome of coronary artery disease

Jguirim-Souissi

Jelassi²,

Slimani³

et al. 2011

Coronary Artery Disease

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These findings showed a trend of the GG-A haplotype of MMP-1 G-1607GG/MMP-12 A1082G towards the prediction of future clinical events in patients with CAD and suggested a possible importance of these loci in the prediction of the prognosis of CAD. Studies with large sample size are warranted to better investigate this association, as MMP genotyping could aid in identifying patients who are likely to have unfavourable prognosis.

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“…However, the imbalanced degradation and synthesis of the extracellular matrix persists in advanced lesions, particularly in plaques with disruption [17]. 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 vulnerable plaques [18]. However, plaques from MMP-9 knockout mice are associated with a lower macrophage content compared with those of wild type mice [19], suggesting a primary role of MMP-9 in macrophage migration and activity.…”

Section: Discussionmentioning

confidence: 99%

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

Baroncini

Nakao

Ramos³

et al. 2011

Thrombosis J

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BackgroundMature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components.ObjectivesTo investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue.MethodsThirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified.ResultsFifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue.ConclusionsMMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.

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Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms

Cited by 20 publications

References 30 publications

The Complementary Effects of Atorvastatin and Exercise Treatment on the Composition and Stability of the Atherosclerotic Plaques in ApoE Knockout Mice

The Complementary Effects of Atorvastatin and Exercise Treatment on the Composition and Stability of the Atherosclerotic Plaques in ApoE Knockout Mice

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the outcome of coronary artery disease

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

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