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1.
Int J Cardiovasc Imaging ; 35(9): 1745-1753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312997

RESUMO

No data exist whether statins have robust anti-inflammatory effects of atherosclerotic plaques primarily during the early treatment period or continuously throughout use. This prospective three time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) study of the carotid artery assessed anti-inflammatory effects of statin during the early treatment period (initiation to 3 months) and late treatment period (3 months to 1 year) and their correlation with lipid and inflammatory profile changes during a year of therapy. Nine statin-naïve stable angina patients with inflammatory carotid plaques received 20 mg/day atorvastatin after undergoing initial 18F-FDG PET/CT scanning of carotid arteries and ascending thoracic aorta, and then completed serial 18F-FDG PET/CT imaging at 3 and 12 months whose data were analyzed. The primary outcome was the inter-scan percent change in target-to-background ratio (ΔTBR) within the index vessel. At 3 months of atorvastatin treatment, mean serum low-density lipoprotein cholesterol (LDL-C) level decreased by 36.4% to < 70 mg/dL (p = 0.001) and mean serum high-density lipoprotein cholesterol level increased to > 40 mg/dL (p = 0.041), with both maintained with no further reduction up to 1 year (p = 0.516 and 0.715, respectively) while mean serum high sensitivity C-reactive protein level only numerically decreased (p = 0.093). The index vessel ΔTBR showed continuous plaque inflammation reduction over 1 year, by 4.4% (p = 0.015) from the initiation to 3rd months and 6.2% (p = 0.009) from 3rd months to 1 year, respectively, without correlation with lipid profile changes. The ΔTBR of the bilateral carotid arteries and ascending aorta also continuously decreased from 3 months to 1 year. Three time point 18F-FDG PET/CT imaging demonstrates that statin's anti-inflammatory effect continues throughout its use up to 1 year, even though yielding stable below-target plasma LDL-C levels at 3 months.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aorta Torácica/efeitos dos fármacos , Doenças da Aorta/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Fluordesoxiglucose F18/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
2.
Expert Rev Clin Pharmacol ; 12(8): 771-780, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31269825

RESUMO

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.


Assuntos
Aterosclerose/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Animais , Aspirina/administração & dosagem , Aterosclerose/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/induzido quimicamente , Humanos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacologia , Prevenção Secundária/métodos
3.
J Zoo Wildl Med ; 50(2): 482-486, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260220

RESUMO

A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.


Assuntos
Aterosclerose/veterinária , Bloqueio Atrioventricular/veterinária , Encefalopatias/veterinária , Cardiopatias/veterinária , Hipertensão/veterinária , Lagartos , Animais , Aterosclerose/patologia , Bloqueio Atrioventricular/patologia , Encefalopatias/etiologia , Encefalopatias/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Hipertensão/complicações , Masculino
4.
Adv Clin Chem ; 91: 163-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331488

RESUMO

Pentraxin 3 (PTX3) is involved in vascular inflammation and endothelial dysfunction through various mechanisms. Until now, most studies confirmed an important link between PTX3 and endothelial dysfunction and identified several pathogenetic pathways. PTX3 modulates inflammatory cells, thus stimulating vascular inflammation. Within endothelial cells, it decreases nitric oxide (NO) synthesis, inhibits cell proliferation and alters their functions. PTX3 blocks the effect of fibroblast growth factor 2 (FGF2) by making a molecular complex with these molecules inactivating them. However, there are substances like the tumor necrosis factor-inducible gene 6 protein (TSG-6) that block the PTX3-FGF2 interaction. Interacting with P-selectin, it promotes vascular inflammatory response and endothelial dysfunction. PTX3 also increases the matrix metalloproteinases synthesis directly or by blocking NO synthesis. From a clinical point of view, PTX3 positively correlates with arterial hypertension, flow mediated dilation and, with intima media thickness. Therefore, the involvement of PTX3 in the pathogenesis and evaluation of endothelial dysfunction is clear, and it may become a biomarker in this direction, but further studies are needed to determine its reliability in this direction. Last but not least, PTX3 could become an effective therapeutic target for preventing this dysfunction, but further research needs to be conducted.


Assuntos
Aterosclerose/metabolismo , Proteína C-Reativa/metabolismo , Células Endoteliais/metabolismo , Inflamação/metabolismo , Componente Amiloide P Sérico/metabolismo , Aterosclerose/etiologia , Aterosclerose/patologia , Proteína C-Reativa/genética , Regulação da Expressão Gênica , Humanos , Componente Amiloide P Sérico/genética
5.
Chem Biol Interact ; 311: 108772, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31351049

RESUMO

Atherosclerosis is a common type of cardiovascular disease (CVD), remaining one of the leading causes of global death. Tripartite motif-containing 28 (TRIM28) is a member of TRIM family that has been found to be involved in atherosclerosis. However, the role of TRIM28 in atherosclerosis remains unknown. This study aimed to investigate the effects of TRIM28 on the phenotypic switching of human aortic smooth muscle cells (HASMCs), which is considered as a fundamental event during the development of atherosclerosis. The results showed that TRIM28 was highly expressed in human atherosclerotic tissues, as well in cultured HASMCs stimulated by platelet-derived growth factor subunit B homodimer (PDGF-BB). Knockdown of TRIM28 by transfection with siRNA targeting TRIM28 (si-TRIM28) significantly suppressed the PDGF-BB-induced cell proliferation and migration of HASMCs. Besides, knockdown of TRIM28 inhibited the expressions of matrix metalloproteinase (MMP)-2 and MMP-9. The VSMC markers including α-smooth muscle actin (α-SMA), calponin and SM22α were upregulated in TRIM28 knocked down HASMCs. Furthermore, knockdown of TRIM28 blocked PDGF-BB-induced NF-κB activation in HASMCs. Collectively, knockdown of TRIM28 prevented PDGF-BB-induced phenotypic switching of HASMCs, which might be mediated by the regulation of NF-κB signaling pathway.


Assuntos
Becaplermina/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteína 28 com Motivo Tripartido/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Proteínas dos Microfilamentos/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Transcrição RelA/metabolismo , Proteína 28 com Motivo Tripartido/antagonistas & inibidores , Proteína 28 com Motivo Tripartido/genética , Regulação para Cima/efeitos dos fármacos
6.
Life Sci ; 232: 116590, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228514

RESUMO

Endothelial cell (EC) apoptosis is fundamental for the pathophysiology of atherosclerosis, in which microRNAs (miRNAs) emerge as critical regulators. miR-122 has been shown to regulate the apoptosis of various cell types, however, whether miR-122 is associated with atherosclerosis and EC apoptosis remains unknown. In this study, we found that miR-122 expression was increased in the aortic ECs of ApoE-/- mice fed with a high-fat diet (HFD), as compared to normal-diet (ND), implying a potential association between miR-122 elevation and atherogenesis. In addition, in vitro, miR-122 expression was also induced in human aortic ECs (HAECs) by the treatment of oxidized low-density lipoprotein (ox-LDL), a common atherogenic factor. Functionally, miR-122 knockdown suppressed ox-LDL-induced apoptosis of HAECs, suggesting a pro-apoptotic role of miR-122 in HAECs under this pro-atherogenic condition. Further evidence revealed that the X-linked inhibitor-of-apoptosis protein (XIAP) was directly targeted and suppressed by miR-122 in HAECs, and more importantly, XIAP knockdown diminished miR-122 effect on apoptosis, thus establishing XIAP as a prominent target that mediates miR-122 regulation of the apoptosis of HAECs. Together, these results may identify miR-122 as a novel regulator in EC apoptosis, which offers it as a possible target for therapeutic interventions of atherosclerosis.


Assuntos
Aterosclerose/metabolismo , MicroRNAs/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Animais , Aorta/metabolismo , Apolipoproteínas E/metabolismo , Apoptose/fisiologia , Aterosclerose/genética , Aterosclerose/patologia , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , MicroRNAs/genética , Transdução de Sinais , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
7.
Life Sci ; 232: 116601, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31252000

RESUMO

AIMS: Tet1, Tet2, and interleukin-6 (IL-6) have been linked to atherosclerosis. Whether Tet3 has a relationship with atherosclerosis and IL-6 was unknown. This study aims to determine the link between Tet3 and IL-6, and the role of Tet3 in prenatal hypoxia-induced atherosclerosis in offspring rats. MAIN METHODS: Pregnant rats were divided into hypoxia and control group. Their male offspring were tested at 20 months old. Hematoxylin-eosin staining and transmission electron microscopic staining were used. Gene mRNA and protein levels were measured with q-PCR or Western blotting. Cell viability and migration was tested with MTT or cell scratch assay. 5-hmC and 5-mC expression were obtained by qGlucMS-PCR; 5-hmC and 5-mC activity were obtained by dot blotting. KEY FINDINGS: Chronic prenatal hypoxia increased Tet3 and IL-6 expression, and decreased Tet3 activity in offspring rats. GlucMS-qPCR showed the percentage of 5-hmC was significantly up-regulated in the promoter of IL-6 in both the rats and cells. Moreover, 5-hmC percentage also was increased in the A7r5 cells transfected with Tet3. Furthermore, Tet3 promoted proliferation and migration of A7r5 cells. However, Tet3 was not sensitive to acute hypoxia, while influenced by HIF-1α DNA element. SIGNIFICANCE: Tet3 enhanced IL-6 expression though up-regulating 5-hmC percentage in the IL-6 promoter.


Assuntos
Aterosclerose/metabolismo , Desoxicitidina/análogos & derivados , Dioxigenases/metabolismo , Hipóxia/metabolismo , Interleucina-6/biossíntese , Animais , Aterosclerose/genética , Aterosclerose/patologia , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Desoxicitidina/metabolismo , Epigênese Genética , Feminino , Hipóxia/genética , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Oxigenases de Função Mista/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ativação Transcricional , Regulação para Cima
8.
J Photochem Photobiol B ; 196: 111508, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152936

RESUMO

Cardiovascular malady (CVM) isn't just the essential driver of death in created western nations, yet additionally, its sickness load is expanding in China. Oxidative pressure initiated free radicals assume a basic job in cell forms involved in atherosclerosis and numerous other heart illnesses. Quercetin (QC) is cancer prevention agents medicate which is demonstrated that successfully secures against CVMs. Encapsulations of medications in polymeric materials are generally utilized in creating continued and controllable medication discharge, or to keep away from the debasement of non-discharged medications. In this present work, a novel arrangement of polymeric superparamagnetic nano-silica (SiN)@poly(lactic-co-glycolic acid) (PLGA) (SiN@PLGA) stacked with QC was created by means of lyophilization method so as to improve poor watery solvency and steadiness of the medication with the point of preventing atherosclerosis. The aftereffects of SEM investigation and the checking, TEM affirmed the manufacture of the circular nanocomposite, smooth surface, and thin size dispersion. The discharge profile of QC from the particles was explored by deciding the medication sum discharged at explicit interims for by iridescence. The data got from this investigation encourages the structure and manufacture of nanocomposite as conceivable conveyance frameworks for epitome, assurance and controlled arrival of the flavonoid QC which is expecting to secure against CVMs.


Assuntos
Nanocompostos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Quercetina/química , Dióxido de Silício/química , Animais , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Nanocompostos/toxicidade , Quercetina/metabolismo , Quercetina/uso terapêutico
9.
Int J Mol Sci ; 20(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060209

RESUMO

Legumain, a recently discovered cysteine protease, is increased in both carotid plaques and plasma of patients with carotid atherosclerosis. Legumain increases the migration of human monocytes and human umbilical vein endothelial cells (HUVECs). However, the causal relationship between legumain and atherosclerosis formation is not clear. We assessed the expression of legumain in aortic atheromatous plaques and after wire-injury-induced femoral artery neointimal thickening and investigated the effect of chronic legumain infusion on atherogenesis in Apoe-/- mice. We also investigated the associated cellular and molecular mechanisms in vitro, by assessing the effects of legumain on inflammatory responses in HUVECs and THP-1 monocyte-derived macrophages; macrophage foam cell formation; and migration, proliferation, and extracellular matrix protein expression in human aortic smooth muscle cells (HASMCs). Legumain was expressed at high levels in atheromatous plaques and wire injury-induced neointimal lesions in Apoe-/- mice. Legumain was also expressed abundantly in THP-1 monocytes, THP-1 monocyte-derived macrophages, HASMCs, and HUVECs. Legumain suppressed lipopolysaccharide-induced mRNA expression of vascular cell adhesion molecule-1 (VCAM1), but potentiated the expression of interleukin-6 (IL6) and E-selectin (SELE) in HUVECs. Legumain enhanced the inflammatory M1 phenotype and oxidized low-density lipoprotein-induced foam cell formation in macrophages. Legumain did not alter the proliferation or apoptosis of HASMCs, but it increased their migration. Moreover, legumain increased the expression of collagen-3, fibronectin, and elastin, but not collagen-1, in HASMCs. Chronic infusion of legumain into Apoe-/- mice potentiated the development of atherosclerotic lesions, accompanied by vascular remodeling, an increase in the number of macrophages and ASMCs, and increased collagen-3 expression in plaques. Our study provides the first evidence that legumain contributes to the induction of atherosclerotic vascular remodeling.


Assuntos
Aterosclerose/metabolismo , Aterosclerose/patologia , Cisteína Endopeptidases/metabolismo , Remodelação Vascular , Animais , Apoptose , Aterosclerose/etiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisteína Endopeptidases/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Matriz Extracelular/metabolismo , Células Espumosas/metabolismo , Células Espumosas/patologia , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Neointima/metabolismo , Neointima/patologia
10.
DNA Cell Biol ; 38(7): 597-606, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31095428

RESUMO

Mitochondria are highly dynamic organelles beyond powerhouses of a cell. These components also play important roles in cell homeostasis by regulating cell function and phenotypic modulation. Atherosclerosis is the leading cause of morbidity and mortality in developed and developing countries. Mitochondrial dysfunction has been increasingly associated with the initiation and progression of atherosclerosis by elevating the production of reactive oxygen species and mitochondrial oxidative stress damage, mitochondrial dynamics dysfunction, and energy supply. In this review, we describe the progression of the link between mitochondrial dysfunction and atherosclerosis and its potential regulation mechanisms.


Assuntos
Aterosclerose/metabolismo , Mitocôndrias/metabolismo , Animais , Aterosclerose/patologia , Endotélio Vascular/metabolismo , Humanos , Ativação de Macrófagos , Músculo Liso Vascular/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Wiad Lek ; 72(4): 584-588, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055537

RESUMO

OBJECTIVE: Introduction: Atherosclerosis is a trigger in the development of cardiovascular disease. Complications of atherosclerosis give reason to search for new criteria, diagnostic concepts, treatment methods and active preventive measures. The aim of our work is to study of the structural changes in the intima-media complex of the common carotid artery, pro-inflammatory cytokines (TNF-α, IL-6) secreted by mononuclear cells; the level of the intercellular adhesion molecule (according to sICAM-1), the level of the C-peptide of the blood, as well as the study of the relationship between these factors affecting the development of atherosclerosis. PATIENTS AND METHODS: Materials and methods: In the group of 110 patients are studied the levels of secretion of TNF-α, IL-6, the soluble intercellular adhesion molecule-1, the level of blood C-peptide, performed of duplex scanning of the brachiocephalic vessels, studied of biopsy of the skin. RESULTS: Results and conclusions: In the group of patients with atherosclerosis and the accompanying metabolic syndrome, endothelial activation is noted under the influence of risk factors (hyperinsulinemia, arterial hypertension, hypercholesterolemia), accompanied with the activation of mononuclear cells (with marked hyperproduction of proinflammatory cytokines (IL-6) and thickening of the intima-media complex of the common carotid artery with an increase in body weight. Patients with metabolic syndrome develop microangiopathy (edema of endothelial cells, thickening and reduplication of the basement membranes, focal reaction of the pericytes).


Assuntos
Aterosclerose/patologia , Peptídeo C/sangue , Leucócitos Mononucleares/metabolismo , Aterosclerose/metabolismo , Biomarcadores , Artérias Carótidas , Espessura Intima-Media Carotídea , Citocinas/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Túnica Íntima
12.
ACS Appl Mater Interfaces ; 11(17): 15316-15321, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30969098

RESUMO

Nanoparticles have been assessed in preclinical models of atherosclerosis for detection of plaque complexity and treatment. However, their successful clinical translation has been hampered by less than satisfactory plaque detection and lack of a general strategy for assessing the translational potential of nanoparticles. Herein, nanoparticles based on comb-co-polymer assemblies were synthesized through a modular construction approach with precise control over the conjugation of multiple functional building blocks for in vivo evaluation. This high level of design control also allows physicochemical properties to be varied in a controllable fashion. Through conjugation of c-atrial natriuretic factor (CANF) peptide and radiolabeling with 64Cu, the 64Cu-CANF-comb nanoparticle was assessed for plaque imaging by targeting natriuretic peptide clearance receptor (NPRC) in a double-injury atherosclerosis model in rabbits. The prolonged blood circulation and enhanced binding capacity of 64Cu-CANF-comb nanoparticles provided sensitive and specific imaging of NPRC overexpressed in atherosclerotic lesions by positron emission tomography at intervals during the progression of the disease. Ex vivo tissue validation using autoradiography and immunostaining on human carotid endarterectomy specimens demonstrated specific binding of 64Cu-CANF-comb to human NPRC receptors. Taken together, this study not only shows the potential of NPRC-targeted 64Cu-CANF-comb nanoparticles for increased sensitivity to an epitope that increases during atherosclerosis plaque development but also provides a useful strategy for the general design and assessment of the translational potential of nanoparticles in cardiovascular imaging.


Assuntos
Nanopartículas/química , Tomografia por Emissão de Pósitrons , Animais , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Fator Natriurético Atrial/química , Fator Natriurético Atrial/metabolismo , Radioisótopos de Cobre/química , Modelos Animais de Doenças , Artéria Femoral/diagnóstico por imagem , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Coelhos , Compostos Radiofarmacêuticos/química , Receptores do Fator Natriurético Atrial/química , Receptores do Fator Natriurético Atrial/metabolismo
13.
Environ Toxicol ; 34(7): 825-835, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30963716

RESUMO

Galectin-3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin-3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1), a receptor for oxLDL uptake, contributes to oxLDL-induced endothelial dysfunction. Whether galectin-3 induces endothelial dysfunction through modulation of LOX-1-mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin-3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX-1. Incubation of HUVECs with galectin-3 increased the expression of LOX-1 in RNA and protein levels. In addition, the expression of LOX-1 induced by oxLDL was promoted by galectin-3. However, pretreatment of LOX-1 antibody reduced LOX-1 mRNA expression level in cells with oxLDL plus galectin-3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen-activated protein kinases followed by nuclear factor kappa B (NF-κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL-8 release were also aggravated in cells treated with galectin-3 combined with oxLDL. Compared to cells treated with galectin-3 plus oxLDL group. We found that LOX-1 antibody mitigated NADPH oxidase activity, p-38 up-regulation, NF-κB activation, and proinflammatory responses in cells treated with galectin-3 combined with oxLDL. We conclude that galectin-3 enhances endothelial LOX-1 expression and propose a new mechanism by which galectin-3 may promote endothelial dysfunction by inducing inflammation via LOX-1/ROS/p38/NF-κB-mediated signaling pathway.


Assuntos
Aterosclerose/induzido quimicamente , Endotélio Vascular/efeitos dos fármacos , Galectina 3/farmacologia , Lipoproteínas LDL/toxicidade , Receptores Depuradores Classe E/fisiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , Sinergismo Farmacológico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Zhongguo Zhong Yao Za Zhi ; 44(2): 235-241, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30989939

RESUMO

In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.


Assuntos
Aterosclerose/tratamento farmacológico , Inflamação , Placa Aterosclerótica/tratamento farmacológico , Trombose/tratamento farmacológico , Aterosclerose/patologia , Citocinas , Fibrose , Humanos , Placa Aterosclerótica/patologia , Trombose/patologia
15.
Environ Pollut ; 249: 482-490, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928520

RESUMO

Epidemiological evidence showed that the particulate matter exposure is associated with atherosclerotic plaque progression, which may be related to foam cell formation, but the mechanism is still unknown. The study was aimed to investigate the toxic effects and possible mechanism of PM2.5 on the formation of macrophage foam cells induced by oxidized low density lipoprotein (ox-LDL). Results showed that PM2.5 induced cytotoxicity by decreasing the cell viability and increasing the LDH level in macrophage foam cells. PM2.5 aggravated the lipid accumulation in ox-LDL-stimulated macrophage RAW264.7 within markedly increasing level of intracellular lipid by Oil red O staining. The level of ROS increased obivously after co-exposure to PM2.5 and ox-LDL than single exposure group. In addition, serious mitochondrial damage such as the mitochondrial swelling, cristae rupturing and disappearance were observed in macrophage foam cells. The loss of the mitochondrial membrane potential (MMP) further exacerbated the mitochondrial damage in PM2.5-induced macrophage foam cells. The apoptotic rate increased more severely via up-regulated protein level of Bax, Cyt C, Caspase-9, Caspase-3, and down-regulated that of Bcl-2, indicating that PM2.5 activated the mitochondrial-mediated apoptosis pathway. In summary, our results demonstrated that PM2.5 aggravated the lipid accumulation, mitochondrial damage and apoptosis in macrophage foam cells, suggesting that PM2.5 was a risk factor of atherosclerosis progression.


Assuntos
Apoptose/efeitos dos fármacos , Células Espumosas/patologia , Lipoproteínas LDL/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Material Particulado/toxicidade , Placa Aterosclerótica/patologia , Animais , Aterosclerose/patologia , Caspase 3/biossíntese , Caspase 9/biossíntese , Linhagem Celular , Citocromos c/biossíntese , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Proteína X Associada a bcl-2/biossíntese
16.
J Stroke Cerebrovasc Dis ; 28(6): 1586-1596, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928215

RESUMO

BACKGROUND: Complex aortic plaque is a potential cause of acute ischemic cerebrovascular disease, which needs timely identification. Also as a marker for systemic atherosclerosis, complex aortic plaque may be indicated by significant (≥50%) cervicocephalic atherosclerotic stenosis. We aimed at examining whether age ranges would influence their association to more accurately estimate the risk of having complex aortic plaque in acute ischemic cerebrovascular disease. METHODS: Aortic arch and cervicocephalic arteries were simultaneously evaluated using computed tomography angiography. Middle-aged (45-64 years) and old-aged (65-85 years) acute ischemic cerebrovascular disease patients were divided into 2 groups according to whether there was an aortic arch plaque with thickness of greater than or equal to 4 mm or associated ulcerations or mural thrombus. RESULTS: Old-aged patients (n = 107) had a higher prevalence of complex aortic plaque (67.3% versus 30.9%, P < .001) than those middle aged (n = 178). Among middle-aged patients, the presence of extracranial significant atherosclerotic stenosis (adjusted odd ratio = 2.89, 95% confidence interval: 1.42-5.86) rather than intracranial ones independently predicted complex aortic plaque. Regarding the extent of significant cervicocephalic atherosclerotic stenosis, the presence of multi-segment, bilateral, simultaneous extracranial and intracranial, and simultaneous anterior and posterior circulation ones were independent indicators for complex aortic plaque in the middle-aged subgroup (adjusted odd ratio = 2.42, 2.05, 2.26, 2.14, respectively). By contrast, no statistical correlation of complex aortic plaque and significant cervicocephalic atherosclerotic stenosis was found among old-aged patients. CONCLUSION: Considering the ranges of age was important to more precisely predict complex aortic plaque with significant cervicocephalic atherosclerotic stenosis in acute ischemic cerebrovascular disease.


Assuntos
Aorta Torácica/patologia , Doenças da Aorta/epidemiologia , Aterosclerose/epidemiologia , Isquemia Encefálica/epidemiologia , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/epidemiologia , Artérias Cerebrais/patologia , Arteriosclerose Intracraniana/epidemiologia , Placa Aterosclerótica , Acidente Vascular Cerebral/epidemiologia , Artéria Vertebral/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Aortografia/métodos , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Isquemia Encefálica/diagnóstico , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Artérias Cerebrais/diagnóstico por imagem , China/epidemiologia , Angiografia por Tomografia Computadorizada , Estudos Transversais , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Dados Preliminares , Prevalência , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Artéria Vertebral/diagnóstico por imagem
17.
Int Heart J ; 60(3): 746-755, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31019169

RESUMO

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.


Assuntos
Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Macrófagos/patologia , Monócitos/patologia , Placa Aterosclerótica/patologia , Animais , Apolipoproteínas E/administração & dosagem , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Colesterol/sangue , Modelos Animais de Doenças , Hiperlipidemias/complicações , Hiperlipidemias/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/ultraestrutura , Triglicerídeos/sangue
18.
Methods Mol Biol ; 1951: 153-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30825151

RESUMO

Monocytes are circulating cells imperative to the response against pathogens. Upon infection, they are quickly recruited to the affected tissue where they can differentiate into specialized phagocytes and antigen-presenting cells. Additionally, monocytes play a vital role in chronic inflammation, where they can promote and enhance inflammation or induce its resolution. There are two major subsets of monocytes, "inflammatory" and "nonclassical," which are believed to have distinct functions. In atherosclerosis, both types of monocytes are constantly recruited to lesions, where they contribute to plaque formation and atherosclerosis progression. Surprisingly, these cells can also be recruited to lesions and promote resolution of atherosclerosis. Tracking these cells in various disease stages may inform about the dynamic changes occurring in the inflamed and resolving tissues. In this chapter we will discuss methods for differential labeling of the two monocyte subsets in order to examine their dynamics in inflammation.


Assuntos
Aterosclerose/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Animais , Aterosclerose/patologia , Biomarcadores , Movimento Celular , Progressão da Doença , Imunofluorescência , Humanos , Imunofenotipagem , Macrófagos/patologia , Microesferas , Monócitos/patologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Coloração e Rotulagem
19.
Pathol Res Pract ; 215(5): 1083-1088, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30926224

RESUMO

Atherosclerosis is a systemic disease affecting the whole arterial tree of the human body, and it is the leading cause of cardiovascular diseases.Vascular smooth muscle cells (VSMCs) have been identified to play a key role in the development of atherosclerosis. MicroRNAs (miRNAs) are a group of endogenous small non-coding RNAs, and they play a critical role in many biological processes including regulating cell proliferation, migration and apoptosis. However, till now, the expression and role of miR-133b in atherosclerosis remain largely unknown. Therefore, our purpose was to investigate the expression and role of miR-133b in atherosclerosis and to explore the underlying mechanism. The results showed that miR-133b was down-regulated in the blood and vascular plaque tissues of rabbits with atherosclerosis. Matrix metallopeptidase 9 (MMP-9) was a direct target of miR-133b. In addition, our data indicated that miR-133b mimic could significantly inhibit rVSMC cell proliferation activity, migration ability and induce cell apoptosis compared with the control group, and all these effects were reversed by MMP-9-plasmid. Taken together, these findings highlight an important role for miR-133b/MMP-9 axis in atherosclerosis. And miR-133b might be a valuable clinical marker and therapeutic target for atherosclerosis.


Assuntos
Aterosclerose/patologia , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Animais , Aterosclerose/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Coelhos
20.
Turk J Med Sci ; 49(2): 604-609, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889943

RESUMO

Background/aim: In the present study we aimed to investigate whether the earlobe crease (ELC) might provide predictive information about white matter intensities (WMIs) in the brain that reflect brain aging. Materials and methods: A total of 350 individuals examined from January 2016 to July 2016 were screened. Patients with known demyelinating white matter disease, neurodegenerative disorders, cerebrovascular event history, or brain tumors were excluded from the study. Finally, 285 cases were included in the study. The four-point cerebral intensity classification system of Fazekas was used in the evaluation of the brain. The ELC was evaluated by inspection. Results: A total of 285 patients were enrolled consecutively. The incidence of WMI was significantly higher in patients with ELC than the others. Age (95% CI: 1.105­1.213, P < 0.001) and ELC (95% CI: 0.098­0.783, P = 0.015) were found as an independent determinants of abnormal WMI. ELC predicted abnormal WMIs with 89% specificity and 62% sensitivity. Conclusion: The presence of an ELC may provide predictive information in terms of detecting abnormal WMIs with prognostic impact in apparently healthy subjects.


Assuntos
Pavilhão Auricular/anormalidades , Voluntários Saudáveis , Substância Branca/anormalidades , Substância Branca/patologia , Adulto , Idoso , Aterosclerose/diagnóstico , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Valor Preditivo dos Testes , Estudos Prospectivos , Rigidez Vascular , Substância Branca/diagnóstico por imagem
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