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1.
BMC Res Notes ; 12(1): 336, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196144

RESUMO

OBJECTIVE: The study was dedicated to investigation of some hemostasis and endothelial dysfunction factors association with probability of presence of vulnerable atherosclerotic plaques in coronary arteries in men with atherosclerosis. RESULTS: The blood levels of factor VII, factor XII and MCP-1 were higher, and concentration of sVCAM-1 lower in men with vulnerable atherosclerotic plaques in the coronary arteries, compared to men who had stable plaques. Have been revealed correlation links between the blood levels of factor II, factor XII, MCP-1 and the presence of vulnerable atherosclerotic plaques in the coronary arteries. Results of logistic regression analysis showed that the relative risk of present of vulnerable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII and MCP-1.


Assuntos
Aterosclerose/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Endotélio Vascular/fisiopatologia , Hemostasia , Placa Aterosclerótica/fisiopatologia , Idoso , Aterosclerose/sangue , Quimiocina CCL2/sangue , Doença da Artéria Coronariana/sangue , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Endotélio Vascular/metabolismo , Fator XII/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Probabilidade , Protrombina/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
2.
Oxid Med Cell Longev ; 2019: 8134678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080547

RESUMO

Background: There is a crosstalk between endoplasmic reticulum stress (ERS) and autophagy, and autophagy could attenuate endoplasmic reticulum stress-mediated apoptosis. Ginkgo biloba leaf extract (GBE) exerts vascular protection functions. The purpose of the present study is to investigate the role of autophagy in diabetic atherosclerosis (AS) and the effect of GBE on autophagy and ERS. Methods: Network pharmacology was utilized to predict the targets and pathways of the active chemical compounds of Gingko biloba leaf to attenuate AS. ApoE-/- mice were rendered diabetic by intraperitoneal ingestion with streptozotocin combined with a high-fat diet. The diabetic mice were divided into five groups: model group, atorvastatin group, rapamycin group, and low- and high-dose GBE groups. Serum and tissue markers of autophagy or ERS markers, including the protein expression, were examined. Results: The mammalian target of rapamycin (mTOR) and NF-κB signaling pathways were targeted by the active chemical compounds of GBE to attenuate AS predicted by network pharmacology. GBE reduced the plaque area/lumen area and the plaque lipid deposition area/intimal area and inhibited the expressions of CD68, MMP2, and MMP9. Rapamycin and GBE inhibited the expression of mTOR and SQSTM1/p62 which increased in the aorta of diabetic mice. In addition, GBE reduced the expression of ERS markers in diabetic mice. GBE reduced the serum lipid metabolism levels, blood glucose, and inflammatory cytokines. Conclusion: Impaired autophagy and overactive endoplasmic reticulum stress contributed to diabetic atherosclerosis. mTOR inhibitor rapamycin and GBE attenuated diabetic atherosclerosis by inhibiting ERS via restoration of autophagy through inhibition of mTOR.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Autofagia , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse do Retículo Endoplasmático , Extratos Vegetais/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Animais , Aterosclerose/sangue , Autofagia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal , Colágeno/metabolismo , Citocinas/sangue , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Transdução de Sinais
3.
J Clin Lab Anal ; 33(6): e22891, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30955225

RESUMO

BACKGROUND: Acute cerebral infarction (ACI) is seriously harmful to human health worldwide. However, at present, the risk of disease onset is still not accurately predicted for some people. METHODS: Five hundred and nineteen patients with ACI and 300 healthy controls were included in this study. We divided the patients into three groups according to the results of cervical artery contrast-enhanced ultrasound. Ninety-five patients were in the CAS without plaque group, 108 patients were in the stable plaque group, and 316 patients were in the unstable plaque group. TC, TG, HDL-C, LDL-C, and sdLDL-C were measured in all subjects. RESULTS: The level of small dense low-density lipoprotein cholesterol (sdLDL-C) in the ACI group was significantly higher than that in the control group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for ACI (OR = 1.067, 95% CI: 1.041-1.093, P < 0.001); serum sdLDL-C was significantly higher in the unstable plaque group than in the stable plaque group and plaque-free group (P < 0.05, P < 0.001); serum sdLDL-C was also higher in the stable plaque group than the plaque-free group (P < 0.001). Logistic regression analysis showed that sdLDL-C was an independent risk factor for unstable carotid plaques (OR = 1.053, 95% CI: 1.038-1.068, P < 0.001); Spearman correlation analysis showed that sdLDL-C test results were positively correlated with carotid plaque stability (r = 0.363, P < 0.001). CONCLUSION: Small dense low-density lipoprotein cholesterol is an independent risk factor for the onset of ACI and may be an early serum marker for this disease.


Assuntos
Infarto Cerebral/patologia , LDL-Colesterol/sangue , Placa Aterosclerótica/patologia , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Infarto Cerebral/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Curva ROC , Triglicerídeos/sangue
4.
Int J Mol Sci ; 20(7)2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959963

RESUMO

Lifestyle choices play a significant role in the etiology of atherosclerosis. Male Apoe-/- mice that develop spontaneous atherosclerotic lesions were fed 0%, 0.3%, and 0.4% mangosteen extracts, composed largely of α-mangostin (MG), for 17 weeks. Body weight gains were significantly decreased in both MG-treated groups compared to the control, but the general condition remained good throughout the study. The levels of total cholesterol (decreased very-low-density lipoprotein in lipoprotein profile) and triglycerides decreased significantly in the MG-treated mice in conjunction with decreased hepatic HMG-CoA synthase and Fatty acid transporter. Additionally, increased serum lipoprotein lipase activity and histopathology further showed a significant reduction in atherosclerotic lesions at both levels of MG exposure. Real-time PCR analysis for macrophage indicators showed a significant elevation in the levels of Cd163, an M2 macrophage marker, in the lesions of mice receiving 0.4% MG. However, the levels of Nos2, associated with M1 macrophages, showed no change. In addition, quantitative immunohistochemical analysis of macrophage subtypes showed a tendency for increased M2 populations (CD68⁺/CD163⁺) in the lesions of mice given 0.4% MG. In further analysis of the cytokine-polarizing macrophage subtypes, the levels of Interleukin13 (Il13), associated with M2 polarization, were significantly elevated in lesions exposed to 0.4% MG. Thus, MG could suppress the development of atherosclerosis in Apoe-/- mice, possibly through an M2 macrophage-mediated mechanism.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Macrófagos/metabolismo , Xantonas/uso terapêutico , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Colesterol/sangue , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Xantonas/química
5.
Clin Cardiol ; 42(6): 618-628, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30993750

RESUMO

BACKGROUND: The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described. HYPOTHESIS: EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI. METHODS: Data on coronary artery plaques from 121 patients who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no-EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI. RESULTS: We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low-density lipoprotein cholesterol concentration, triglyceride concentration, and high-density lipoprotein cholesterol concentration). OFDI data from 60 patients were analyzed in this study. The EPA group had significantly lower mean lipid index (818 ± 806 vs 1574 ± 891) and macrophage grade (13.5 ± 5.9 vs 19.3 ± 7.4) but higher mean minimum fibrous cap thickness (109.2 ± 55.7 vs 81.6 ± 36.4 µm) than the no-EPA group (P = 0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P = 0.043 and 0.024, respectively). CONCLUSION: This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Ácido Eicosapentaenoico/uso terapêutico , Placa Aterosclerótica/terapia , Tomografia de Coerência Óptica/métodos , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Intervenção Coronária Percutânea/métodos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
6.
Angiology ; 70(8): 737-746, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31030528

RESUMO

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle-brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Inflamação/sangue , Doença Arterial Periférica/sangue , Idoso , Aterosclerose/diagnóstico , Aterosclerose/terapia , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco
7.
Int Heart J ; 60(3): 569-576, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31019178

RESUMO

Blood glucose variability is considered to be one of the risk factors for coronary heart disease, and there is growing evidence that blood glucose fluctuation is closely related to the characteristics of plaques. The aim of the study was to investigate the influence of blood glucose variability on the vulnerability of culprit plaques in elderly non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients.Coronary angiography and VH-IVUS were applied to evaluate the components of culprit plaque in NSTE-ACS patients. CGMS monitoring was performed for 72 hours and blood glucose variability was assessed by glycemic excursions (MAGE), absolute means of daily differences (MODD), postprandial glycemic excursions (PPGE), and the largest amplitude of glycemic excursions (LAGE). An oxidative stress indicator (urinary 8-iso-PGF2α) was also tested.Eighty two elderly NSTE-ACS patients were enrolled in this study. Higher glucose variability was associated with the increased culprit plaque instability. MODD was positively correlated with urinary 8-iso-PGF2α. PPGE and urinary 8-iso-PGF2α were independent risk factors for percent fibrous and necrotic volume in culprit plaques (PPGE: ß = -0.340, P = 0.024; urinary 8-iso-PGF2α: ß = -0.294, P = 0.013).Blood glucose variability is positively related to oxidative stress. With an increase in blood glucose variability, the instability of criminal plaques in elderly NSTE-ACS patients increased.


Assuntos
Síndrome Coronariana Aguda/sangue , Glicemia/análise , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Placa Aterosclerótica/diagnóstico por imagem , Síndrome Coronariana Aguda/complicações , Idoso , Angiografia Coronária , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Estresse Oxidativo , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Período Pós-Prandial
8.
Medicine (Baltimore) ; 98(17): e15194, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027064

RESUMO

INTRODUCTION: While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree, on the extension of ventricular remodeling and scaring, has not been clarified yet. MATERIALS AND METHODS: The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study. The main purpose of this trial is to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). One hundred patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms will be enrolled in the study. The level of systemic inflammation will be evaluated based on the serum biomarker levels (hs-CRP, matrix metalloproteinases, interleukin-6) in the acute phase of the myocardial infarction (MI) and at 1 month. Pan-coronary plaque vulnerability will be assessed based on serum biomarkers known to be associated with increased plaque vulnerability (V-CAM or I-CAM) and at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features of all coronary plaques. Myocardial viability and remodeling will be assessed based on 3D speckle tracking echocardiography associated with dobutamine infusion and LGE-CMR associated with post-processing imaging methods. The study population will be categorized in 2 subgroups: subgroup 1 - subjects with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl), and subgroup 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP < 3 mg/dl). Study outcomes will consist in the rate of post-infarction heart failure development and the major adverse events (MACE) rate. CONCLUSION: VIABILITY is the first prospective study designed to evaluate the influence of infarct-related inflammatory response on several major determinants of post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling.


Assuntos
Doença da Artéria Coronariana/imunologia , Inflamação/imunologia , Placa Aterosclerótica/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Remodelação Ventricular/imunologia , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Inflamação/sangue , Inflamação/diagnóstico por imagem , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
9.
Gastroenterol Hepatol ; 42(6): 362-371, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30952463

RESUMO

INTRODUCTION: Chronic infection with hepatitis C virus is a risk factor for developing atheromatous plaques, although the possible effect of virus clearance is unknown. Our aim was to determine whether or not subclinical atheromatosis improved and there was any modification in the composition of the plaques 12 months after eradication of hepatitis C virus by direct-acting antiviral agents. MATERIALS AND METHODS: Prospective study that included 85 patients with chronic hepatitis C virus infection in different stages of fibrosis who were on direct-acting antiviral agents. Patients with a cardiovascular history, diabetes and kidney disease were excluded. An arterial ultrasound (carotid and femoral) was performed to diagnose atheromatous plaques (defined as intima-media thickness ≥1.5mm) and the composition (percentage of lipids, fibrosis and calcium with HEMODYN4 software) was analysed at the beginning of the study and 12 months after stopping the therapy. RESULTS: After follow-up no changes were detected in the intima-media thickness (0.65mm vs. 0.63mm, P=.240) or in the presence of plaques (65.9% vs 71.8%, P=.063). There was also no significant change in their composition or affected vascular territory, with an increase in blood lipid profile (P<.001) after 12 months of treatment. These results were confirmed in subgroups by severity of liver disease. DISCUSSION: The eradication of hepatitis C virus by direct-acting antiviral agents does not improve the atheroma plaques and nor does it vary their composition, regardless of liver fibrosis. More prospective studies are needed to evaluate residual cardiovascular risk after virus eradication.


Assuntos
Antivirais/uso terapêutico , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Adulto , Idoso , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/virologia , Espessura Intima-Media Carotídea , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/virologia , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Risco , Fatores de Tempo
10.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934954

RESUMO

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.


Assuntos
Angiografia Coronária , Doença das Coronárias/enzimologia , Lipoproteína(a)/sangue , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença das Coronárias/sangue , Doença das Coronárias/metabolismo , Feminino , Humanos , Lipoproteína(a)/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Software
11.
Thromb Res ; 177: 130-135, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897531

RESUMO

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025.


Assuntos
Estenose das Carótidas/sangue , Fibrinogênio/análise , Fibrinogênios Anormais/análise , Placa Aterosclerótica/sangue , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Feminino , Hemostasia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos
12.
Biomed Res Int ; 2019: 3793840, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863777

RESUMO

Background: The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. Methods: 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. Results: Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P<0.05), in comparison with the CAS group, whereas effects were not significant between the Normal-CRM group and Blank-control group. In comparison with the CAS group, the positive expression of CD34 and CD68 in the CAS-CRM group increased significantly (P<0.05). Conclusion: CRM therapy may increase the vulnerability of carotid plaque in rabbits with severe CAS.


Assuntos
Oclusão com Balão/efeitos adversos , Proteína C-Reativa/genética , Doenças das Artérias Carótidas/cirurgia , Manipulação da Coluna/efeitos adversos , Placa Aterosclerótica/cirurgia , Animais , Antígenos CD34/genética , Proteína C-Reativa/metabolismo , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiopatologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/fisiopatologia , Lesões das Artérias Carótidas/cirurgia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , Coelhos
13.
Am J Cardiol ; 123(10): 1565-1571, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851941

RESUMO

Statins are widely used to lower cholesterol and to reduce cardiovascular events. Whether all statins have similar effects on plaque stabilization is unknown. We aimed to investigate coronary plaque response to treatment with different statins that result in similar lipid reduction using serial multimodality intracoronary imaging. Patients with de novo coronary artery disease requiring intervention were randomized to rosuvastatin 10mg (R10) or atorvastatin 20mg (A20) daily. Optical coherence tomography and intravascular ultrasound were performed at baseline, 6 months, and 12 months. Untreated nonculprit plaques were analyzed by optical coherence tomography for thin-cap fibroatheroma, minimum fibrous cap thickness, lipid arc, and lipid length. Total and percent atheroma volume, respectively were analyzed by intravascular ultrasound. Forty-three patients completed the protocol (R10: 24 patients, 31 plaques; A20: 19 patients, 30 plaques). The decrease in serum lipids was similar. From baseline to 6 months to 12 months, minimum fibrous cap thickness increased in the R10 group (61.4 ± 15.9 µm to 120.9 ± 57.9 µm to 171.5 ± 67.8 µm, p <0.001) and the A20 group (60.8 ± 18.1 µm to 99.2 ± 47.7 µm to 127.0± 66.8 µm, p <0.001). Prevalence of thin-cap fibroatheroma significantly decreased in the R10 and A20 groups (-48% and -53%, respectively, p <0.001 for intragroup comparisons). Only the R10 group had a decrease in macrophage density (-23%, p = 0.04) and microvessels (-12%, p = 0.002). Total atheroma volume decreased in the R10 group (109.2 ± 62.1 mm3 to 101.8 ± 61.1 mm3 to 102.5 ± 62.2 mm3, p = 0.047) but not in the A20 group (83.3 ± 48.5mm3 to 77.6 ± 43.0 mm3 to 77.9 ± 48.6 mm3, p = 0.07). In conclusion, although both statins demonstrated similar reductions in lipid profiles, the rosuvastatin group showed more rapid and robust plaque stabilization, and regression of plaque volume compared to the atorvastatin group.


Assuntos
Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Rosuvastatina Cálcica/uso terapêutico , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Estudos Prospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
14.
Arterioscler Thromb Vasc Biol ; 39(3): 523-529, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30727753

RESUMO

Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P<0.001): per log unit (relative risk, 1.05); Lp(a)≥30 mg/dL (relative risk, 1.16); and Lp(a)≥50 mg/dL (relative risk, 1.20). Lp(a) levels over 50 mg/dL were associated with a higher plaque score at baseline in whites (all P<0.001) and Hispanics ( P=0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P=0.03) and higher plaque scores (all P<0.001) over the 9.4-year follow-up. Race-based differences between whites and black participants were significant for cross-sectional associations and for carotid plaque score following the 9.4 year study period. Conclusions- Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.


Assuntos
Doenças das Artérias Carótidas/etnologia , Grupos de Populações Continentais , Lipoproteína(a)/sangue , Placa Aterosclerótica/etnologia , Grupo com Ancestrais do Continente Africano , Idoso , Idoso de 80 Anos ou mais , Antropometria , Americanos Asiáticos , Doenças das Artérias Carótidas/sangue , Comorbidade , Estudos Transversais , Diabetes Mellitus/etnologia , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Hispano-Americanos , Humanos , Hipertensão/etnologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Prevalência , Risco , Fumar/etnologia , Fatores Socioeconômicos
15.
J Neurosurg Sci ; 63(4): 388-393, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26899301

RESUMO

BACKGROUND: Cerebral branch atheromatous disease (BAD) are more likely to experience progressing stroke and neurological deterioration compared with lacunar infarction, although these small vessels occlusions are difficult to discriminate in acute phase of ischemic stroke. Advanced glycation end products including pentosidine have been implicated in atherosclerosis, and were associated with atheroma plaque progression. However, little is known about a relationship between serum pentosidine and small vessels occlusion. METHODS: Serum pentosidine levels were measured in 56 patients (BAD: N.=21; lacunar: N.=35) with small vessels occlusion among consecutive 208 patients with acute ischemic stroke at initial hospitalization as well as other risk factors of stroke. Univariate and multivariate logistic regression analyses were performed to analyze relationship between risk factors including pentosidine and small vessels occlusion. Sensitivity and selectivity of pentosidine to discriminate BAD from lacunar were calculated. RESULTS: Serum pentosidine was significantly higher in BAD group than lacunar group (0.081±0.081 µg/mL and 0.046±0.043 µg/mL, P<0.05). In the univariate logistic regression analyses, BAD was significantly related to high serum pentosidine (P=0.01), absence of dyslipidemia (P=0.04), and worse outcome measured by modified Rankin Scale (P=0.03). Multivariate logistic regression analysis showed that only high level of serum pentosidine was the independent risk factor for BAD (P=0.03). Sensitivity and specificity were 90% and 44%, respectively. CONCLUSIONS: High level of serum pentosidine in acute phase of stroke was associated with BAD, which led to worse outcome among patients with small vessels occlusion.


Assuntos
Arginina/análogos & derivados , Isquemia Encefálica/sangue , Lisina/análogos & derivados , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Progressão da Doença , Feminino , Humanos , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
16.
Clin Cardiol ; 42(1): 39-46, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30318598

RESUMO

BACKGROUND: Atherosclerosis is an inflammatory disease. Many studies demonstrated that hyperglycemia is not only increased inflammatory response, but also is a cause of atherosclerosis, implying that glucose metabolic status may be an important stratification factor when analyzing the relationship between inflammatory levels and subclinical carotid atherosclerosis. The aim of the present study is to assess the relationship between inflammatory levels and subclinical carotid atherosclerosis, stratified by different glucose metabolic status in a general population. METHODS: An assessment was performed in 7975 participants living in Tianjin, China. In the present study, we examined subclinical carotid atherosclerosis, as defined by increased carotid intima-media thickness [IMT] and plaques. Measurements were performed using a carotid artery B-mode ultrasound system. The glucose metabolic status was defined by the criteria of the American Diabetes Association, and high-sensitivity C-reactive protein (hs-CRP) as an inflammatory indicator, was measured by immunoturbidimetric assay. Multiple logistic models were used to assess a stratified relationship between hs-CRP levels and subclinical carotid atherosclerosis. Strata were defined according to glucose metabolic status. RESULTS: The prevalence of increased IMT and plaques were 27.3% and 21.3%, respectively. The adjusted odds ratios (95% confidence interval) for IMT across hs-CRP quartiles were as follows: 1.00 (reference), 1.10(0.88-1.38), 1.08(0.86-1.35) and 1.32(1.06-1.66) in blood glucose-normal subjects; 1.00 (reference), 1.33(0.92-1.91), 1.33(0.93-1.91), and 1.59(1.10-2.30) in prediabetic subjects; 1.00 (reference), 0.94(0.54-1.62), 1.17(0.65-2.12) and 0.98(0.55-1.76) in diabetic subjects, respectively. Similar results were observed for plaques. CONCLUSIONS: Our results suggest that inflammatory levels are differently related to subclinical carotid atherosclerosis by the different glucose metabolic status.


Assuntos
Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/sangue , Hiperglicemia/sangue , Placa Aterosclerótica/sangue , Biomarcadores/sangue , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/etiologia , Prevalência , Fatores de Risco , Ultrassonografia Doppler em Cores
17.
Mol Biol Rep ; 46(1): 1317-1321, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30421129

RESUMO

Toll-like receptor 4 (TLR4)/prostaglandine synthetase 2 (PTGS2) signaling plays a relevant role in atherosclerotic plaque vulnerability. The purpose of this study was to check the gene expression of 6 genes participating to TLR4/PTGS2 signaling (TLR4, PTGS2, ACSL4, PTGER3, PTGER4, and EPRAP) in carotid plaques and blood samples from the same individual and to evaluate these genes as biomarker of plaque progression. We investigated differential gene expression by qRT-PCR in 62 atherosclerotic patients' carotid plaques and corresponding blood sample. A very weak or no correlation was observed in the overall population or analyzing asymptomatic patients. These analyzed genes are most likely not suitable for inclusion in the clinical routine as biomarkers of plaque instability.


Assuntos
Artérias Carótidas/patologia , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/genética , Regulação da Expressão Gênica , Placa Aterosclerótica/genética , Transdução de Sinais , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética , Idoso , Feminino , Humanos , Masculino , Placa Aterosclerótica/sangue , Transdução de Sinais/genética
18.
Clin Chim Acta ; 490: 69-76, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30550937

RESUMO

BACKGROUND: The levels of plasma sLR11, released from intimal SMCs, are positively associated with intima-media thickness (IMT) in asymptomatic subjects. We have evaluated the yet unknown pathological significance of sLR11 for plaque conditions in patients with carotid artery stenosis. METHODS: The presence of LR11 in carotid plaques was investigated using autopsy specimens. A clinical ultrasonography study for elucidating relationships between sLR11 and plaque condition was performed in 46 patients. RESULTS: Immunohistochemistry showed high levels of LR11 in SMCs within thickened intima and at the media-intima border of atherosclerotic carotid plaques. The levels of sLR11 in patients were clearly elevated compared to healthy controls. Univariate analysis of sLR11 revealed significant positive correlation with plaque score and a tendency to correlate with the stenotic fraction. Univariate and multiple regression analyses of plaque scores showed that sLR11, maximum IMT, and HDL-cholesterol independently determined plaque score. Finally, univariate analysis of initial sLR11 levels for changes in imaging markers after one-year follow-up showed that initial sLR11 levels significantly correlated with stenotic fraction progression. CONCLUSIONS: The levels of sLR11, abundantly expressed in carotid atherosclerotic plaques, are highly associated with increased plaque score. sLR11 levels may be predictive of plaque conditions in patients with advanced carotid atherosclerosis.


Assuntos
Estenose das Carótidas/complicações , Movimento Celular , Proteínas Relacionadas a Receptor de LDL/sangue , Proteínas Relacionadas a Receptor de LDL/química , Proteínas de Membrana Transportadoras/sangue , Proteínas de Membrana Transportadoras/química , Miócitos de Músculo Liso/patologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/complicações , Idoso de 80 Anos ou mais , Diferenciação Celular , Feminino , Humanos , Masculino , Placa Aterosclerótica/patologia
19.
Biomed Pharmacother ; 109: 1445-1453, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551396

RESUMO

INTRODUCTION: We have investigated the possible effects and mechanism of atorvastatin, a statin, and/or probucol, a powerful antioxidant used to lower cholesterol before 1995, on the atherosclerosis development. METHODS: Apolipoprotein-E-deficient (ApoE-/-) mice fed with the high fat diet were randomly divided into 3 groups (n = 10/each group): Placebo, Atorvastatin (10 mg/ kg/d), and atorvastatin (10 mg/kg/d) plus probucol (10 mg/kg/d) groups. C57BL/6 J mice were fed with normal diet as the control group (n = 10). Animals were sacrificed 10 weeks after the intervention. To evaluate the experimental atherosclerosis, blood tests were used for measuring serum lipoprotein profile, Western blots for endoplasmic reticulum (ER) stress protein expression, H&E staining for plaque lesions, immunohistology for macrophages, inflammatory cytokines, innate immune receptor TLR-4, transcription factor NF-κB, and atherosclerosis plaques. RESULTS: Compared with the control group, ApoE-/- mice in the placebo group showed with the significantly (p < 0.05) higher levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and oxidized low density lipoprotein (ox-LDL), PERK, GRP78, CHOP, IL-1ß, TNF-α and NF-κB, but with the lower levels of high-density lipoprotein cholesterol (HDL) and TLR-4, and also the increase in macrophages and the aortic media collagen, and the decrease in the elastic fibers (p < 0.01). Treatment with atorvastatin recovered all these features (p < 0.05 or p < 0.01) near to the levels in the control group. In addition, the combination of atorvastatin and probucol has shown the slightly stronger effect than the use of atorvastatin alone without statistical significances when comparing most bio-markers of atherosclerosis, but with significant differences in the reduction of the plaque lesion areas and macrophages (p < 0.05). CONCLUSIONS: Atorvastatin and/or probucol suppresses ER stress and increase the level of TLR-4, which lowers NF-κB, resulting in the recovery of atherosclerosis in the ApoE-/- mouse model.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Atorvastatina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Probucol/farmacologia , Animais , Antioxidantes/metabolismo , Aterosclerose/sangue , Aterosclerose/metabolismo , Colesterol/sangue , Citocinas/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo
20.
J Thorac Imaging ; 34(1): 26-32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30142137

RESUMO

PURPOSE: Recent advances in image quality of coronary computed tomographic angiography (cCTA) have enabled improved characterization of coronary plaques. Thus, we investigated the association between quantitative morphological plaque markers obtained by cCTA and serum lipid levels in patients with suspected or known coronary artery disease. MATERIALS AND METHODS: We retrospectively analyzed data of 119 statin-naive patients (55±14 y, 66% men) who underwent clinically indicated cCTA between January 2013 and February 2017. Patients were subdivided into a plaque and a no-plaque group. Quantitative and morphologic plaque markers, such as segment involvement score, segment stenosis score, remodeling index, napkin-ring sign, total plaque volume, calcified plaque volume, and noncalcified plaque volume (NCPV) and plaque composition, were analyzed using a semiautomated plaque software prototype. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratio, and triglycerides were determine in both groups. RESULTS: Higher age (61±11 y vs. 52±14 y, P<0.0001) and a higher likelihood of male gender (77% vs. 56%, P<0.0001) were observed in the plaque group. Differences in lipid levels were neither observed for differentiation between plaque presence or absence, nor after subcategorization for plaque composition. LDL serum levels >160 mg/dL correlated with higher NCPV compared with patients with LDL between 100 and 160 mg/dL (112 vs. 27 mm, P=0.037). Other markers were comparable between the different groups. CONCLUSION: Statin-naive patients with known or suspected coronary artery disease did not show differences in lipid levels related to plaque composition by cCTA. Patients with plaques tended to be men and were significantly older. High LDL levels correlated with high NCPV.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Lipídeos/sangue , Placa Aterosclerótica/diagnóstico por imagem , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Estudos Retrospectivos , Fatores Sexuais , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem
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