共查询到20条相似文献，搜索用时 15 毫秒
1.
Bo Li Yunhe Zhao Hui Liu Bin Meng Jitao Wang Tianjun Qi Hui Zhang Tao Li Peiqing Zhao Hui Sun Jia Xu Haibo Song Zhe Dong Fengshuang An 《PloS one》2016,11(2)
Objectives
Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.Methods
In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E–deficient (ApoE−/−) mice, and lentivirus expressing visfatin (lenti-visfatin) was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC) and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Results
Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Conclusions
Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index. 相似文献2.
Petros Moustardas Nikolaos P. E. Kadoglou Michalis Katsimpoulas Alkistis Kapelouzou Nikolaos Kostomitsopoulos Panayotis E. Karayannacos Alkiviadis Kostakis Christos D. Liapis 《PloS one》2014,9(9)
Aim
This 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.Methods
Forty 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.Results
All 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.Conclusion
The 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. 相似文献3.
Azhar Abbas P?l Aukrust David Russell Kirsten Krohg-S?rensen Trine Alm?s Dorte Bundgaard Vigdis Bjerkeli Ellen Lund Sagen Annika E. Michelsen Tuva B. Dahl Sverre Holm Thor Ueland Mona Skjelland Bente Halvorsen 《PloS one》2014,9(1)
Background
Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.Methods
Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.Results
Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.Conclusion
Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms. 相似文献4.
5.
Helene Skj?t-Arkil Rikke E. Clausen Lars M. Rasmussen Wanchun Wang Yaguo Wang Qinlong Zheng Hans Mickley Lotte Saaby Axel C. P. Diederichsen Jess Lambrechtsen Fernando J. Martinez Cory M. Hogaboam MeiLan Han Martin R. Larsen Arkadiusz Nawrocki Ben Vainer Dorrit Krustrup Marina Bj?rling-Poulsen Morten A. Karsdal Diana J. Leeming 《PloS one》2013,8(6)
Background
Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Methods
Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position ‘552 in elastin by matrix metalloproteinase (MMP) −9/−12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position ‘441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI), no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) was compared to controls.Results
ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01). Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01).Conclusions
The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question. 相似文献6.
Dominik von Elverfeldt Constantin von zur Muhlen Kristina Wiens Irene Neudorfer Andreas Zirlik Mirko Meissner Peg Tilly Anne-Laure Charles Christoph Bode Karlheinz Peter Jean-Etienne Fabre 《PloS one》2012,7(9)
Background
Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI) of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture.Methods
An antibody targeting ligand-induced binding sites (LIBS) on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO) to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE−/− mice (60 weeks-old) were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO.Results
LIBS-MPIO injected animals showed a significant signal extinction (p<0.05) in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01).Conclusion
in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE−/− mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions. 相似文献7.
Shuang-shuang Wang Si-wang Hu Qing-hua Zhang Ai-xiang Xia Zhi-xin Jiang Xiao-min Chen 《PloS one》2015,10(8)
Background and objectives
Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Subjects and methods
Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.Results
Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.Conclusions
Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis. 相似文献8.
Background
The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma.Aim
To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up.Material and Methods
428 men and 438 women, aged 45–69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein.Results
53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low.Conclusion
Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events. 相似文献9.
Brigit den Adel Linda M. van der Graaf Gustav J. Strijkers Hildo J. Lamb Robert E. Poelmann Louise van der Weerd 《PloS one》2013,8(3)
Background
High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent.Methods and Results
We applied a 2D-FLASH retrospective-gated CINE MRI method at 9.4T to characterize atherosclerotic plaques and vessel wall distensibility in the aortic arch of aged ApoE−/− mice after injection of a contrast agent. The method enabled detection of contrast enhancement in atherosclerotic plaques in the aortic arch after I.V. injection of micelles and iron oxides resulting in reproducible plaque enhancement. Both contrast agents were taken up in the plaque, which was confirmed by histology. Additionally, the retrospective-gated CINE method provided images of the aortic wall throughout the cardiac cycle, from which the vessel wall distensibility could be calculated. Reduction in plaque size by statin treatment resulted in lower contrast enhancement and reduced wall stiffness.Conclusions
The retrospective-gated CINE MRI provides a robust and simple way to detect and quantify contrast enhancement in atherosclerotic plaques in the aortic wall of ApoE−/− mice. From the same scan, plaque-related changes in stiffness of the aortic wall can be determined. In this mouse model, a correlation between vessel wall stiffness and atherosclerotic lesions was found. 相似文献10.
Objectives
Little data are available regarding coronary plaque composition and semi-quantitative scores in individuals with diabetes; the extent to which diabetes may affect the presence and extent of Coronary Artery Calcium (CAC) needs more evaluation. Considering that this information may be of great value in formulating preventive interventions in this population, we compared these findings in individuals with diabetes to those without.Methods
Multi-Detector Computed Tomographic (MDCT) images of 861 consecutive patients with diabetes who were referred to Los Angeles Biomedical Research Institute from January 2000 to September 2012, were evaluated using a 15–coronary segment model. All 861 patients underwent calcium scoring and from these; 389 had coronary CT angiography (CTA). CAC score was compared to 861 age, sex and ethnicity matched controls without diabetes after adjustment for Body Mass Index (BMI), family history of coronary artery disease, hyperlipidemia, hypertension and smoking. Segment Involvement Score (SIS; the total number of segments with any plaque), Segment Stenosis Score (SSS; the sum of maximal stenosis score per segment), Total Plaque Score (TPS; the sum of the plaque amount per segment) and plaque compositionwere compared to 389 age, sex and ethnicity matched controls without diabetes after adjustment for BMI, family history of coronary artery disease, hyperlipidemia, hypertension and smoking.Results
Diabetes was positively correlated to the presence and extent of CAC (P<0.0001 for both). SIS, SSS and TPS were significantly higher in those with diabetes (P<0.0001). Number of mixed and calcified plaques were significantly higher in those with diabetes (P = 0.018 and P<0.001 respectively) but there was no significant difference in the number of non-calcified plaques between the two groups (P = 0.398).Conclusions
Patients with diabetes have higher CAC and semi-quantitative coronary plaque scores compared to the age, gender and ethnicity matched controls without diabetes after adjustment for cardiovascular risk factors. Since mixed plaque is associated with worse long-term clinical outcomes, these findings support more aggressive preventive measures in this population. 相似文献11.
Sílvia Collado Elisabeth Coll Carlos Nicolau Mercedes Pons Josep M Cruzado Julio Pascual Aleix Cases 《PloS one》2015,10(6)
Background
To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.Methods
Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.Results
83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).Conclusions
The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies. 相似文献12.
Reyhan Nergiz-Unal Judith M. E. M. Cosemans Marion A. H. Feijge Paola E. J. van der Meijden Robert F. Storey J. J. J. van Giezen Mirjam G. A. oude Egbrink Johan W. M. Heemskerk Marijke J. E. Kuijpers 《PloS one》2010,5(4)
Background
In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y12 receptors. However, such models do not predict involvement of P2Y12 in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y12 in thrombus formation on (collagen-containing) atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis.Methodology
Plaques in the carotid arteries from Apoe −/− mice were acutely ruptured by ultrasound treatment, and the thrombotic process was monitored via intravital fluorescence microscopy. Thrombus formation in vitro was assessed in mouse and human blood perfused over collagen or plaque material under variable conditions of shear rate and coagulation. Effects of two reversible P2Y12 blockers, ticagrelor (AZD6140) and cangrelor (AR-C69931MX), were investigated.Principal Findings
Acute plaque rupture by ultrasound treatment provoked rapid formation of non-occlusive thrombi, which were smaller in size and unstable in the presence of P2Y12 blockers. In vitro, when mouse or human blood was perfused over collagen or atherosclerotic plaque material, blockage or deficiency of P2Y12 reduced the thrombi and increased embolization events. These P2Y12 effects were present at shear rates >500 s−1, and they persisted in the presence of coagulation. P2Y12-dependent thrombus stabilization was accompanied by increased fibrin(ogen) binding.Conclusions/Significance
Platelet P2Y12 receptors play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques. This P2Y12 function is restricted to high shear flow conditions, and is preserved in the presence of coagulation. 相似文献13.
Marina Beltrami-Moreira Amélie Vromman Galina K. Sukhova Eduardo J. Folco Peter Libby 《PloS one》2016,11(3)
Aims
Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms α and β) have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1α and IL-1β in the induction of MMP-3 and other matrix-remodeling enzymes in human cells.Methods and Results
Human primary vascular smooth muscle cells (VSMCs) and carotid endarterectomy specimens were stimulated with equimolar concentrations of IL-1α or IL-1β and analyzed protease expression by immunoblot and ELISA. Either IL-1α or IL-1β increased the expression of pro-MMP-3 in VSMCs, facilitated VSMC migration through Matrigel, and induced MMP-3 production in specimens from atheromatous plaques. VSMCs also secreted MMP-1 and Cathepsin S (CatS) upon stimulation with IL-1α or IL-1β. IL-1 isoforms similarly increased MMP-1 and MMP-9 expression in carotid endarterectomy specimens. We examined the expression of MMP-3 and IL-1 isoforms by immunostaining of carotid atheromata, calculated the % positive areas, and tested associations by linear regression. MMP-3 colocalized with IL-1 isoforms in atheromata. MMP-3+ area in plaques positively associated with IL-1α+ (R2 = 0.61, P<0.001) and with IL-1β + areas (R2 = 0.68, P<0.001). MMP-3+ area within atheroma also associated with CD68+ area, but not with α-smooth muscle actin area.Conclusions
Either IL-1α or IL-1β can induce the expression of enzymes implicated in remodeling of the arterial extracellular matrix, and facilitate human VSMC migration in vitro. Human atheromata contain both IL-1 isoforms in association with immunoreactive MMP-3. This redundancy of IL-1 isoforms suggests that selective blocking of one IL-1 isoform should not impair expansive arterial remodeling, a finding with important clinical implications for therapeutic targeting of IL-1 in atherosclerosis. 相似文献14.
Franca Marino Matteo Tozzi Laura Schembri Stefania Ferraro Antonino Tarallo Angela Scanzano Massimiliano Legnaro Patrizio Castelli Marco Cosentino 《PloS one》2015,10(4)
Objectives
Polymorphonuclear neutrophils (PMN) in atherosclerotic plaques have been identified only recently, and their contribution to plaque development is not yet fully understood. In this study, production of elastase, interleukin (IL)-8 and vascular endothelial growth factor (VEGF) by PMN was investigated in subjects with carotid stenosis undergoing carotid endarterectomy (CEA).Methods
The study enrolled 50 patients (Pts) and 10 healthy subjects (HS). Circulating PMN (cPMN) isolated from venous blood (in both Pts and HS) and from plaques (pPMN, in Pts) were cultured, alone or with 0.1 μM fMLP. Elastase, IL-8 and VEGF mRNA were analyzed by real-time PCR. In CEA specimens, PMN were localized by immunohistochemistry.Results
In both Pts cPMN and pPMN, IL-8 mRNA was higher at rest but lower after fMLP (P<0.01 vs HS), and VEGF mRNA was higher both at rest and after fMLP (P<0.01 vs HS), while elastase mRNA was not significantly different. On the contrary, protein production was always higher in cPMN of HS with respect to values measured in cells of Pts. In CEA specimens, CD66b+ cells localized to areas with massive plaque formation close to neovessels. Pts with soft and mix plaques, as defined by computed tomography, did not differ in cPMN or pPMN IL-8, VEGF or elastase mRNA, or in intraplaque CD66b+ cell density. However, Pts with soft plaques had higher white blood cell count due to increased PMN.Conclusions
In Pts with carotid plaques, both circulating and intraplaque PMN produce IL-8, VEGF and elastase, which are crucial for plaque development and progression. These findings suggest mechanistic explanations to the reported correlation between PMN count and cardiovascular mortality in carotid ATH. 相似文献15.
Objective
To study the mechanism of the no-reflow phenomenon using coronary angiography (CAG) and intravascular ultrasound (IVUS).Methods
A total of 120 patients with acute myocardial infarction (AMI) who successfully underwent indwelling intracoronary stent placement by percutaneous coronary intervention (PCI). All patients underwent pre- and post-PCI CAG and pre-IVUS. No-reflow was defined as post-PCI thrombolysis in myocardial infarction (TIMI) grade 0, 1, or 2 flow in the absence of mechanical obstruction. Normal reflow was defined as TIMI grade 3 flow. The pre-operation reference vascular area, minimal luminal cross-sectional area, plaque cross-sectional area, lesion length, plaque volume and plaque traits were measured by IVUS.Results
The no-reflow group was observed in 14 cases (11.6%) and normal blood-flow group in 106 cases (89.4%) based on CAG results. There was no statistically significant difference in the patients’ medical history, reference vascular area (no-flow vs. normal-flow; 15.5 ± 3.2 vs. 16.2 ± 3.3, p> 0.05) and lesion length (21.9 ± 5.1 vs. 19.5 ± 4.8, p> 0.05) between the two groups. No-reflow patients had a longer symptom onset to reperfusion time compared to normal blood-flow group [(6.6 ± 3.1) h vs (4.3 ± 2.7) h; p< 0.05] and higher incidence of TIMI flow grade< 3 (71.4% vs 49.0%, p< 0.05). By IVUS examination, the no-reflow group had a significantly increased coronary plaque area and plaque volume compared to normal blood-flow group [(13.7 ± 3.0) mm2 vs (10.2 ± 2.9) mm2; (285.4 ± 99.8) mm3 vs (189.7 ± 86.4) mm3; p< 0.01]. The presence of IVUS-detected soft plaque (57.1% vs. 24.0%, p< 0.01), eccentric plaque (64.2% vs. 33.7%, p< 0.05), plaque rupture (50.0% vs. 21.2%, p< 0.01), and thrombosis (42.8% vs. 15.3%) were significantly more common in no-reflow group.Conclusion
There was no obvious relationship between the coronary risk factors and no-reflow phenomenon. The symptom onset to reperfusion time, TIMI flow grade before stent deployment, plaque area, soft plaques, eccentric plaques, plaque rupture and thrombosis may be risk factors for the no-reflow phenomenon after PCI. 相似文献16.
Bhairavi Swaminathan Haize Goikuria Reyes Vega Alfredo Rodríguez-Antigüedad Antonio López Medina María del Mar Freijo Koen Vandenbroeck Iraide Alloza 《PloS one》2014,9(12)
Objectives
The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques).Methods
80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools.Results
Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5−fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system−related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients.Conclusions
Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B−associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events. 相似文献17.
Masao Takahashi Susumu Miyazaki Masahiro Myojo Daigo Sawaki Hiroshi Iwata Arihiro Kiyosue Yasutomi Higashikuni Tomofumi Tanaka Daishi Fujita Jiro Ando Hideo Fujita Yasunobu Hirata Issei Komuro 《PloS one》2015,10(3)
Objectives
This study aimed to assess the relation between stent edge restenosis (SER) and the distance from the stent edge to the residual plaque using quantitative intravascular ultrasound.Background
Although percutaneous coronary intervention with drug-eluting stents has improved SER rates, determining an appropriate stent edge landing zone can be challenging in cases of diffuse plaque lesions. It is known that edge vascular response can occur within 2 mm from the edge of a bare metal stent, but the distance to the adjacent plaque has not been evaluated for drug-eluting stents.Methods
A total of 97 proximal residual plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents were retrospectively evaluated to determine the distance from the stent edge to the residual plaque.Results
The SER group had significantly higher PB (59.1 ± 6.1% vs. 51.9 ± 9.1% for non-SER; P = 0.04). Higher PB was associated with SER, with the cutoff value of 54.74% determined using receiver operating characteristic (ROC) curve analysis. At this cutoff value of PB, the distance from the stent edge to the lesion was significantly associated with SER (odds ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725, and the cutoff distance value for predicting SER was 1.0 mm.Conclusion
An interval less than 1 mm from the proximal stent edge to the nearest point with the determined PB cutoff value of 54.74% was significantly associated with SER in patients with residual plaque lesions. 相似文献18.
Kwangsun Yoo Sun Ju Chung Ho Sung Kim Oh-hyeon Choung Young-Beom Lee Mi-Jung Kim Sooyeoun You Yong Jeong 《PloS one》2015,10(4)
Background
Recently, non-motor symptoms of Parkinson’s disease (PD) have been considered crucial factors in determining a patient’s quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.Methods
Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.Results
The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).Conclusions
These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD. 相似文献19.
20.
Maggie Lawrence Jan Pringle Susan Kerr Joanne Booth Lindsay Govan Nicola J. Roberts 《PloS one》2015,10(3)