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1.
Nutr Metab Cardiovasc Dis ; 29(12): 1273-1287, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31669106

RESUMO

AIMS: Dietary pattern (DP) analysis has emerged as a holistic method to understand the effects of food intake on health outcomes. Though dietary intake has been associated with cardiovascular disease, the association of DPs and carotid intima-media thickness (CIMT), a robust early marker of cardiovascular disease progression has not been comprehensively investigated. This study systematically explores the association of a posteriori and a priori DPs and CIMT. DATA SYNTHESIS: Through a systematic search of MEDLINE, CINAHL, and Web of Science, twenty studies that derived DPs using a posteriori or a priori methods with CIMT as an outcome were included. Four cross-sectional studies and 1 cohort paper reported a statistically significant association between increased consumption of 'unhealthy' foods (i.e processed meat, soda drinks and refined grain) and increased CIMT. While four cross-sectional studies reported a statistically significant association of DPs characterized by increased consumption of 'healthy' foods (i.e fruit and vegetables, fish) and decreased CIMT. DPs derived from each study varied depending on derivation method, study design and use of dietary data collection method. CONCLUSION: Findings from this review are generally supportive of a trend between DPs with higher consumption of 'healthy' foods and lower consumption of 'unhealthy' foods and decreased CIMT; however, the association was largely not statistically significant. Evidence was overwhelmingly heterogeneous due to differences seen in DPs based on location and culture, sample characteristics and adjustment for confounders. Long-term prospective observational and interventional studies with standardized sample selection and dietary data collection are needed to significantly establish the role of DPs on CIMT.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Dieta , Comportamento Alimentar , Comportamento de Redução do Risco , Adulto , Idoso , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/prevenção & controle , Dieta/efeitos adversos , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Valor Preditivo dos Testes , Prevenção Primária , Prognóstico , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco
3.
Nutr Metab Cardiovasc Dis ; 29(7): 744-750, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31138498

RESUMO

BACKGROUND AND AIMS: The role of dietary patterns, in cardiovascular diseases has been challenged. The role of breakfast as an element of balance energy intake has gained research interest. However, the effects of dietary patterns related to breakfast consumption on vascular function are unknown. We explored the association of breakfast consumption habits with arterial wall elastic properties and carotid atherosclerosis. METHODS AND RESULTS: In this cross-sectional study we enrolled 2043 inhabitants of the Corinthia region in Greece. Carotid-femoral pulse wave velocity (cf-PWV) was used to assess arterial stiffness. Carotid intima-media thickness (cIMT) was measured and the mean and the maximum cIMT were calculated. According to food frequency questionnaires, breakfast contribution in total daily energy intake (>20%; 5-20% and <5%) was estimated. Subjects were categorized as high-energy breakfast consumers (HeBC), low-energy breakfast consumers (LeBC) and those skipping breakfast (SBf) respectively. From the study population 240 subjects were categorized as HeBC, 897 as LeBC, and 681 as SBf. The mean cf-PWV was significantly higher in subjects SBf compared to LeBC and HeBC (9.35 ± 2.82 m/s vs. 9.09 ± 2.77 m/s vs. 8.76 ± 2.69 m/s, p = 0.02). The mean cIMT was significantly higher in subjects SBf compared to LeBC and HeBC (1.04 ± 0.46 mm vs. 0.99 ± 0.43 mm vs. 0.92 ± 0.39 mm, p = 0.01). Even after adjustment for potential confounders and cardiovascular risk factors SBf subjects have significantly increased mean cIMT and cf-PWV. CONCLUSION: Skipping breakfast has an adverse effect on arterial stiffness and carotid atheromatic burden. Increased breakfast total energy intake may act protectively against atherosclerosis, a finding worth of further pathophysiologic exploration with potential clinical implications.


Assuntos
Desjejum , Doenças das Artérias Carótidas/epidemiologia , Comportamento Alimentar , Rigidez Vascular , Idoso , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Estudos Transversais , Ingestão de Energia , Feminino , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Fatores de Proteção , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco
4.
J Vasc Surg ; 70(3): 927-936.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30777689

RESUMO

OBJECTIVE: Emerging evidence shows that perivascular adipose tissue (PVAT) is crucially involved in inflammation and cardiovascular diseases. However, controversial results have been reported regarding the effect of PVAT in atherosclerosis. This study aimed to determine the role of PVAT in disturbed blood flow (d-flow)-induced carotid plaque formation. METHODS: ApoE-/- male mice underwent partial carotid ligation (PCL) to induce d-flow in the left carotid artery (LCA) and were fed a high-fat diet for 2 weeks. Oil Red O and hematoxylin and eosin stains were used to determine adipose tissue. Thoracic PVAT from ApoE-/- or wild-type female mice were transplanted to the LCA of PCL-treated ApoE-/- mice. Carotid arteries were stained with Sudan IV to detect atherosclerotic lesions. Quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence staining were performed to assess macrophage infiltration. RESULTS: By 2 weeks of the high-fat diet after PCL surgery, de novo adipose tissue was formed around the ligated LCA, where atherosclerotic plaques were also observed. Quantitative real-time reverse transcription polymerase chain reaction analysis of the newly formed PVAT revealed a similar transcription profile to native PVAT. Treatment with bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor γ inhibitor, diminished PVAT formation but increased plaque size and macrophage infiltration. Transplantation of thoracic PVAT from wild-type mice (PVAT-TWT) rather than from ApoE-/- mice (PVAT-TApoE-/-) nearly abrogated LCA plaque macrophage content without affecting plaque size. Mechanistically, PVAT-TApoE-/- showed higher messenger RNA levels of inflammatory cytokines compared with PVAT-TWT. CONCLUSIONS: Our findings suggest that regulated PVAT formation may confer protection against atherosclerosis-prone shear stress, probably through attenuation of focal inflammation.


Assuntos
Tecido Adiposo/fisiopatologia , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Placa Aterosclerótica , Tecido Adiposo/metabolismo , Animais , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/prevenção & controle , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Fluxo Sanguíneo Regional , Estresse Mecânico
5.
Circulation ; 139(1): 101-114, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29970364

RESUMO

BACKGROUND: Hydrogen sulfide (H2S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and proatherogenic conditions. METHODS: Endothelial cell CSE knockout mice were generated, and lung endothelial cells were studied in vitro (gene expression, protein sulfhydration, and monocyte adhesion). Mice were crossed onto the apolipoprotein E-deficient background, and atherogenesis (partial carotid artery ligation) was monitored over 21 days. CSE expression, H2S bioavailability, and amino acid profiling were also performed with human material. RESULTS: The endothelial cell-specific deletion of CSE selectively increased the expression of CD62E and elevated monocyte adherence in the absence of an inflammatory stimulus. Mechanistically, CD62E mRNA was more stable in endothelial cells from CSE-deficient mice, an effect attributed to the attenuated sulfhydration and dimerization of the RNA-binding protein human antigen R. CSE expression was upregulated in mice after partial carotid artery ligation and in atheromas from human subjects. Despite the increase in CSE protein, circulating and intraplaque H2S levels were reduced, a phenomenon that could be attributed to the serine phosphorylation (on Ser377) and inhibition of the enzyme, most likely resulting from increased interleukin-1ß. Consistent with the loss of H2S, human antigen R sulfhydration was attenuated in atherosclerosis and resulted in the stabilization of human antigen R-target mRNAs, for example, CD62E and cathepsin S, both of which are linked to endothelial cell activation and atherosclerosis. The deletion of CSE from endothelial cells was associated with the accelerated development of endothelial dysfunction and atherosclerosis, effects that were reversed on treatment with a polysulfide donor. Finally, in mice and humans, plasma levels of the CSE substrate l-cystathionine negatively correlated with vascular reactivity and H2S levels, indicating its potential use as a biomarker for vascular disease. CONCLUSIONS: The constitutive S-sulfhydration of human antigen R (on Cys13) by CSE-derived H2S prevents its homodimerization and activity, which attenuates the expression of target proteins such as CD62E and cathepsin S. However, as a consequence of vascular inflammation, the beneficial actions of CSE-derived H2S are lost owing to the phosphorylation and inhibition of the enzyme.


Assuntos
Aterosclerose/enzimologia , Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/enzimologia , Cistationina gama-Liase/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Células Endoteliais/enzimologia , Sulfeto de Hidrogênio/metabolismo , Placa Aterosclerótica , Idoso , Idoso de 80 Anos ou mais , Animais , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/prevenção & controle , Catepsinas/metabolismo , Adesão Celular , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Cistationina gama-Liase/deficiência , Cistationina gama-Liase/genética , Modelos Animais de Doenças , Progressão da Doença , Proteína Semelhante a ELAV 1/genética , Células Endoteliais/patologia , Feminino , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Fosforilação , Processamento de Proteína Pós-Traducional , Transdução de Sinais
6.
J Am Heart Assoc ; 7(23): e010405, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30482079

RESUMO

Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.


Assuntos
Doenças das Artérias Carótidas/prevenção & controle , Estilo de Vida Saudável , Doenças Assintomáticas , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Dieta/efeitos adversos , Exercício , Feminino , Estilo de Vida Saudável/fisiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Estados Unidos/epidemiologia
7.
Clin Exp Rheumatol ; 36 Suppl 112(3): 61-67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30156537

RESUMO

OBJECTIVES: The higher incidence of atherosclerosis and cardiovascular disease (CVD) in patients with systemic autoimmune diseases cannot be attributed exclusively to traditional risk factors for CVD. Antibodies to oxidised Low Density Lipoprotein (ox-LDL) seem to have a crucial role in atherogenesis. METHODS: Sera from 63 consecutive patients with primary Sjögren's syndrome (pSS), 121 with systemic lupus erythematosus (SLE), 79 with rheumatoid arthritis (RA) and 26 apparently healthy individuals were evaluated for the presence of antibodies to ox-LDL by ELISA. The femoral and/or carotid intima media thickness (IMT) and plaque formation as well as traditional CVD risk factors and disease-related features were recorded for all study participants. RESUKTS: Anti-ox-LDL antibody levels were significantly reduced in SS and RA patients, but not in SLE patients, compared to their healthy counterparts. Subsequently, SS patients were divided into two groups according to antibody levels to ox-LDL, using as cut off the median of each group studied. SS patients with high titres of antibodies to ox-LDL displayed higher rates of autoantibodies to Ro/SSA and La/SSB antigens, purpura, low complement levels and increased SS activity index. On the other hand, the high anti-ox-LDL group was characterised by reduced rates of carotid and/or femoral plaque after adjusting for potential confounders (OR [95%CI]: 0.14 [0.03-0.72]). Such associations were not shown in all other groups included in the study. CONCLUSIONS: These findings suggest that antibodies to ox-LDL, possibly resulting from B cell hyperactivity, might exert a protective role in the development of atherosclerosis among primary SS patients.


Assuntos
Autoanticorpos/imunologia , Doenças das Artérias Carótidas/imunologia , Artéria Femoral , Lipoproteínas LDL/imunologia , Doença Arterial Periférica/imunologia , Síndrome de Sjogren/imunologia , Anticorpos Antinucleares/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Proteínas do Sistema Complemento/análise , Ensaio de Imunoadsorção Enzimática , Artéria Femoral/diagnóstico por imagem , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Análise Multivariada , Razão de Chances , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/prevenção & controle , Placa Aterosclerótica , Fatores de Proteção , Fatores de Risco , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico
8.
Neurosci Lett ; 683: 54-60, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-29928953

RESUMO

Subcortical ischemic vascular dementia caused by chronic cerebral hypoperfusion due to small-artery disease is a common subtype of vascular dementia, which is recognized as the second most prevalent type of dementia. The aim of this study was to determine the effect of carnosine on white matter damage in corpus striatum. Adult male mice (C57BL/6 strain) were subjected to right unilateral common carotid arteries occlusion (rUCCAO), and treated with carnosine or saline. Klüver-Barrera staining, immunohistochemical analyses, Western blots and neurochemical analysis were performed after rUCCAO. The white matter in corpus striatum was damaged at day 37 after rUCCAO, which was largely rescued by carnosine (200, 500 mg/kg). Carnosine (200, 500 mg/kg) significantly recovered the expression of myelin basic protein, suppressed the activation of microglia and reversed the decrease of 5-hydroxytryptamine and dopamine levels in corpus striatum. Moreover, carnosine (200, 500 mg/kg) significantly inhibited the apoptosis in corpus striatum. These data suggest that carnosine has the neuroprotective effect in corpus striatum on rUCCAO in mice, may be due to its protection of neurotransmitters and inhibition of apoptosis.


Assuntos
Carnosina/uso terapêutico , Doenças das Artérias Carótidas/prevenção & controle , Circulação Cerebrovascular/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Substância Branca/efeitos dos fármacos , Animais , Carnosina/farmacologia , Doenças das Artérias Carótidas/patologia , Circulação Cerebrovascular/fisiologia , Corpo Estriado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Substância Branca/patologia
9.
Nutr Metab Cardiovasc Dis ; 28(8): 830-838, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29853429

RESUMO

BACKGROUND AND AIMS: The relationship between dietary intake and carotid intima media thickness (IMT) and pulse wave velocity (PWV) in individuals with type 1 and type 2 diabetes has not been well studied. We investigated the association between dietary intake and common carotid artery intima media thickness (CCA IMT) and PWV in a cohort with type 1 and type 2 diabetes. METHODS AND RESULTS: A one-year randomised controlled trial was conducted to investigate the effect of improving dietary quality on CCA IMT. These subjects were followed up again approximately 12 months after the completion of the trial (i.e. approximately 24 month since baseline). The study cohort included 87 subjects that had dietary intake and CCA IMT measured at baseline and after a mean of 2.3 years' follow-up. PWV was measured in a subsample of this cohort. Age and baseline mean CCA IMT were strongly associated with mean CCA IMT at 24 months. After adjustment for age and baseline mean CCA IMT, baseline consumption of carbohydrate (r = -0.28; p = 0.01), sugars (r = -0.27; p = 0.01), fibre (r = -0.26; p = 0.02), magnesium (r = -0.25; p = 0.02) and the Alternate Health Eating Index (AHEI) score (r = -0.23; p = 0.03) were inversely associated with mean CCA IMT at 24 months. Mixed linear modelling showed an interaction between mean CCA IMT and AHEI at baseline (p = 0.024). Those who were in the highest AHEI tertile at baseline had greater CCA IMT regression at 24 months compared to those in the lowest tertile, after adjustment for baseline age, BMI, smoking pack years, time since diabetes diagnosis, and mean arterial pressure at baseline (mean -0.043 mm; 95% CI -0.084, -0.003; p = 0.029). CONCLUSIONS: In this prospective analysis greater diet quality at baseline, as measured by the AHEI, was associated with greater CCA IMT regression after approximately two years. This suggests that greater diet quality is associated with better longer term vascular health in individuals with type 1 and type 2 diabetes.


Assuntos
Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Valor Nutritivo , Comportamento de Redução do Risco , Idoso , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Exp Gerontol ; 108: 256-261, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29747013

RESUMO

Several biologically active molecules including nutrients can affect the vascular endothelium which becomes dysfunctional and, as a consequence, predisposes to atherosclerosis. However, the impact of the intake of sodium and polyunsaturated fatty acids on carotid atherosclerosis in a population of elderly women has scarcely been studied. Our aim was to investigate the association between carotid intima-media thickness and atherosclerotic plaque and nutrient intake in asymptomatic elderly women. Carotid atherosclerosis was determined by duplex ultrasound in 108 elderly women. Dietary intake was assessed by a combination of a 24-hour recall and a 7-day food record. A physical examination and laboratory tests were performed. We found an association between the C-IMT and polyunsaturated fatty acid (negative, B = -0.014; p = 0.03; CI -0.027/-0.001) and sodium (positive, r = 0.16; P = 0.09) intake. When linoleic acid was added to the multivariable regression analysis instead of polyunsaturated fatty acids, C-IMT was associated with linoleic acid (B = -0.017; p = 0.02; CI -0.032/-0.003). In normotensive women we found a positive association between the C-IMT and sodium intake. The atherosclerotic plaque prevalence increased with the increase in sodium intake (66% vs 90% Tertile I vs Tertile III; p = 0.02). Iin conclusion, A low salt diet to a level of about 1.5 g/d and a polyunsaturated fatty acid intake of >9 g/d were found to be associate with a low atherosclerotic plaque prevalence in an elderly female population. Sodium and polyunsaturated fatty acids-mediated functional changes of the carotid endothelium may be implicated in atherosclerosis development.


Assuntos
Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Dieta , Ácidos Graxos Insaturados/administração & dosagem , Sódio na Dieta/administração & dosagem , Idoso , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Registros de Dieta , Feminino , Humanos , Modelos Lineares , Análise Multivariada , Placa Aterosclerótica , Fatores de Risco , Ultrassonografia Doppler Dupla
11.
Arterioscler Thromb Vasc Biol ; 38(6): 1368-1380, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29622563

RESUMO

OBJECTIVE: Protease-activated receptor-1 (PAR1) is classically activated by thrombin and is critical in controlling the balance of hemostasis and thrombosis. More recently, it has been shown that noncanonical activation of PAR1 by matrix metalloprotease-1 (MMP1) contributes to arterial thrombosis. However, the role of PAR1 in long-term development of atherosclerosis is unknown, regardless of the protease agonist. APPROACH AND RESULTS: We found that plasma MMP1 was significantly correlated (R=0.33; P=0.0015) with coronary atherosclerotic burden as determined by angiography in 91 patients with coronary artery disease and acute coronary syndrome undergoing cardiac catheterization or percutaneous coronary intervention. A cell-penetrating PAR1 pepducin, PZ-128, currently being tested as an antithrombotic agent in the acute setting in the TRIP-PCI study (Thrombin Receptor Inhibitory Pepducin-Percutaneous Coronary Intervention), caused a significant decrease in total atherosclerotic burden by 58% to 70% (P<0.05) and reduced plaque macrophage content by 54% (P<0.05) in apolipoprotein E-deficient mice. An MMP1 inhibitor gave similar beneficial effects, in contrast to the thrombin inhibitor bivalirudin that gave no improvement on atherosclerosis end points. Mechanistic studies revealed that inflammatory signaling mediated by MMP1-PAR1 plays a critical role in amplifying tumor necrosis factor α signaling in endothelial cells. CONCLUSIONS: These data suggest that targeting the MMP1-PAR1 system may be effective in tamping down chronic inflammatory signaling in plaques and halting the progression of atherosclerosis.


Assuntos
Doenças da Aorta/enzimologia , Aterosclerose/enzimologia , Doenças das Artérias Carótidas/enzimologia , Doença da Artéria Coronariana/enzimologia , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Receptor PAR-1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/prevenção & controle , Linhagem Celular , Peptídeos Penetradores de Células/farmacologia , Ensaios Clínicos Fase II como Assunto , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Fibrinolíticos/farmacologia , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Lipopeptídeos/farmacologia , Masculino , Metaloproteinase 1 da Matriz/sangue , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Oligopeptídeos/farmacologia , Placa Aterosclerótica , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor PAR-1/antagonistas & inibidores , Receptor PAR-1/sangue , Transdução de Sinais , Fator de Necrose Tumoral alfa/sangue , Estados Unidos
12.
J Am Heart Assoc ; 7(8)2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618474

RESUMO

BACKGROUND: Dietary patterns rich in fruits and vegetables are considered to reduce atherosclerotic disease presentation and are reported to be inversely associated with subclinical measures of atherosclerosis, such as carotid artery intima-media thickness (IMT) and plaque. However, the effect of vegetable intake alone, and relationships to specific types of vegetables containing different phytochemical profiles, is important. The aim of this study was to investigate the associations of total vegetable intake and specific vegetables grouped according to phytochemical constituents with common carotid artery IMT (CCA-IMT) and carotid plaque severity in a cohort of older adult women (aged ≥70 years). METHODS AND RESULTS: Total vegetable intake was calculated at baseline (1998) using a validated food frequency questionnaire. Vegetable types included cruciferous, allium, yellow/orange/red, leafy green, and legumes. In 2001, CCA-IMT (n=954) and carotid focal plaque (n=968) were assessed using high-resolution B-mode carotid ultrasonography. Mean (SD) total vegetable intake was 199.9 (78.0) g/d. Women consuming ≥3 servings of vegetables each day had ≈4.6% to 5.0% lower mean CCA-IMT (P=0.014) and maximum CCA-IMT (P=0.004) compared with participants consuming <2 servings of vegetables. For each 10 g/d higher in cruciferous vegetable intake, there was an associated 0.006 mm (0.8%) lower mean CCA-IMT (P<0.01) and 0.007 mm (0.8%) lower maximum CCA-IMT (P<0.01). Other vegetable types were not associated with CCA-IMT (P>0.05). No associations were observed between vegetables and plaque severity (P>0.05). CONCLUSIONS: Increasing vegetables in the diet with a focus on consuming cruciferous vegetables may have benefits for the prevention of subclinical atherosclerosis in older adult women. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615000750583.


Assuntos
Doenças das Artérias Carótidas/prevenção & controle , Artéria Carótida Primitiva/diagnóstico por imagem , Dieta , Placa Aterosclerótica/prevenção & controle , Verduras , Idoso , Doenças das Artérias Carótidas/diagnóstico , Espessura Intima-Media Carotídea , Feminino , Seguimentos , Humanos , Valor Nutritivo , Placa Aterosclerótica/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco
13.
J Hepatol ; 69(1): 18-24, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29505844

RESUMO

BACKGROUND AND AIMS: Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ±â€¯10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ±â€¯0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. RESULTS: All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ±â€¯0.29 mm vs. 0.81 ±â€¯0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. CONCLUSION: HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. LAY SUMMARY: Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.


Assuntos
Antivirais/uso terapêutico , Doenças das Artérias Carótidas/prevenção & controle , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Feminino , Seguimentos , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resposta Viral Sustentada , Resultado do Tratamento
15.
Equine Vet J ; 50(6): 781-786, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29514400

RESUMO

BACKGROUND: Guttural pouch mycosis (GPM) is a cause of nasal discharge, dysphagia and fatal haemorrhage in the horse. OBJECTIVES: To report the complications and success of salpingopharyngeal fistulation in horses with GPM. We hypothesised that creating a direct static opening into the guttural pouch from the pharynx would cause a regression of fungal plaques due to a change in the guttural pouch environment and that this treatment would result in resolution of infection prior to secondary complications. STUDY DESIGN: Retrospective case series. METHODS: The medical records of all horses diagnosed with GPM that were presented to New Bolton Center between the years 2006 and 2017 were examined retrospectively. Seven cases of guttural pouch mycosis treated with salpingopharyngostomy without other surgical intervention were included. Information collected included signalment, presenting complaint, which pouch was affected, size and location of the plaques, laryngeal and pharyngeal function, concurrent medical therapy, location of the fistula, surgical time, time to resolution of clinical signs, time to full resolution of the mycotic plaque, and patency of the salpingopharyngostomy site. RESULTS: Nasal discharge resolved in 10-30 days post-operatively in all cases where nasal discharge was present. The mycotic plaques showed complete resolution at time points ranging from 1 to 6 months post-operatively. No case developed epistaxis or neurological deficits post-operatively that were not present at presentation. MAIN LIMITATIONS: There were differing adjunctive treatments between cases. This technique is not appropriate for horses that have had epistaxis or are currently bleeding. CONCLUSIONS: Salpingopharyngostomy can minimise cost of treatment, be performed on an outpatient basis and provide better exposure of the infected area with few complications. This case series documents seven cases treated with this method that resolved the infection without any further complications of the mycosis.


Assuntos
Doenças das Artérias Carótidas/veterinária , Hemorragia/veterinária , Doenças dos Cavalos/cirurgia , Micoses/veterinária , Faringe/cirurgia , Animais , Doenças das Artérias Carótidas/prevenção & controle , Quimioterapia Adjuvante/veterinária , Endoscopia/métodos , Endoscopia/veterinária , Feminino , Fístula , Hemorragia/prevenção & controle , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/prevenção & controle , Cavalos , Terapia a Laser/veterinária , Masculino , Micoses/tratamento farmacológico , Micoses/cirurgia , Estudos Retrospectivos
16.
Atherosclerosis ; 271: 84-91, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29482038

RESUMO

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) has been associated with an increased risk of atherosclerosis. We aimed to evaluate the progression of carotid intima media thickness (cIMT) in RA patients subject to a cardiovascular treat-to-target intervention. In addition, the presence of the metabolic syndrome (MetS) on cIMT outcomes was evaluated. METHODS: We performed a cohort analysis of FRANCIS, in which RA patients ≤70 years without CVD or diabetes mellitus were randomized for either a treat-to-target intervention or usual care concerning CVD risk factors. MetS was scored at baseline. RESULTS: Three-year data was available in 212 well-controlled RA patients. The treat-to-target intervention resulted in a lower cIMT progression over three years compared to the usual care. However, there was no difference in cIMT at three years between groups. MetS was present in 40.1% of RA patients. Baseline cIMT was significantly higher in RA patients with MetS compared to those without (0.619 (0.112) versus 0.557 (0.104) mm; p < 0.001). After three years, cIMT progression was comparable (0.043 (0.071) versus 0.043 (0.072) mm; p = 0.96). In RA patients with MetS, the presence of plaques increased over three years from 12.9% to 23.5% (p = 0.01). The type of intervention had no effect on cIMT progression in RA patients with MetS. However, in subjects without MetS, treat-to-target resulted in a lower progression. CONCLUSIONS: RA patients with MetS showed an increased CVD risk profile based on both a higher prevalence of CVD risk factors and structural vascular changes. A treat-to-target approach of CVD risk factors reduced cIMT progression only in RA patients without MetS.


Assuntos
Artrite Reumatoide/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Artéria Carótida Primitiva , Síndrome Metabólica/epidemiologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/mortalidade , Artrite Reumatoide/terapia , Doenças Assintomáticas , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/prevenção & controle , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Progressão da Doença , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Placa Aterosclerótica , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Fatores de Tempo , Resultado do Tratamento
17.
Arterioscler Thromb Vasc Biol ; 38(1): 206-217, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29122817

RESUMO

OBJECTIVE: Gene therapy that expresses apo A-I (apolipoprotein A-I) from vascular wall cells has promise for preventing and reversing atherosclerosis. Previously, we reported that transduction of carotid artery endothelial cells with a helper-dependent adenoviral (HDAd) vector expressing apo A-I reduced early (4 weeks) fatty streak development in fat-fed rabbits. Here, we tested whether the same HDAd could provide long-term protection against development of more complex lesions. APPROACH AND RESULTS: Fat-fed rabbits (n=25) underwent bilateral carotid artery gene transfer, with their left and right common carotids randomized to receive either a control vector (HDAdNull) or an apo A-I-expressing vector (HDAdApoAI). Twenty-four additional weeks of high-fat diet yielded complex intimal lesions containing lipid-rich macrophages as well as smooth muscle cells, often in a lesion cap. Twenty-four weeks after gene transfer, high levels of apo A-I mRNA (median ≥250-fold above background) were present in all HDAdApoAI-treated arteries. Compared with paired control HDAdNull-treated arteries in the same rabbit, HDAdApoAI-treated arteries had 30% less median intimal lesion volume (P=0.03), with concomitant reductions (23%-32%) in intimal lipid, macrophage, and smooth muscle cell content (P≤0.05 for all). HDAdApoAI-treated arteries also had decreased intimal inflammatory markers. VCAM-1 (vascular cell adhesion molecule-1)-stained area was reduced by 36% (P=0.03), with trends toward lower expression of ICAM-1 (intercellular adhesion molecule-1), MCP-1 (monocyte chemoattractant protein 1), and TNF-α (tumor necrosis factor-α; 13%-39% less; P=0.06-0.1). CONCLUSIONS: In rabbits with severe hyperlipidemia, transduction of vascular endothelial cells with an apo A-I-expressing HDAd yields at least 24 weeks of local apo A-I expression that durably reduces atherosclerotic lesion growth and intimal inflammation.


Assuntos
Apolipoproteína A-I/genética , Aterosclerose/prevenção & controle , Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/prevenção & controle , Células Endoteliais/metabolismo , Terapia Genética/métodos , Hiperlipidemias/terapia , Animais , Apolipoproteína A-I/biossíntese , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Biomarcadores/sangue , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Hiperlipidemias/sangue , Hiperlipidemias/genética , Molécula 1 de Adesão Intercelular/metabolismo , Lipídeos/sangue , Masculino , Neointima , Placa Aterosclerótica , Coelhos , Transdução Genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
18.
Arterioscler Thromb Vasc Biol ; 37(12): 2364-2369, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28982667

RESUMO

OBJECTIVE: Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. APPROACH AND RESULTS: Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d5 and the nonabsorbable stool marker sitostanol-d4. Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol (r=-0.426; P<0.0001), total cholesterol (r=-0.472; P≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool (r=-0.343; P=0.0012) and was positively correlated with percent cholesterol absorption (r=+0.279; P=0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant (P=0.0008). CONCLUSIONS: Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of reverse cholesterol transport to atherosclerotic disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Colesterol/metabolismo , Eliminação Intestinal , Mucosa Intestinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Colesterol/administração & dosagem , Colesterol/sangue , Fezes/química , Feminino , Humanos , Infusões Intravenosas , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Proteção , Fatores de Risco
19.
Atherosclerosis ; 266: 74-80, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28992467

RESUMO

BACKGROUND AND AIMS: Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness. METHODS: This is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables. RESULTS: Overall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group (p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT (p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT (p = 0.21). CONCLUSIONS: In HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Arginina/análogos & derivados , Doenças das Artérias Carótidas/prevenção & controle , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Adulto , Arginina/sangue , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Distribuição de Qui-Quadrado , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , Humanos , Mediadores da Inflamação/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ohio , RNA Viral/genética , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Viral
20.
J Clin Lipidol ; 11(6): 1372-1382.e4, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28927895

RESUMO

BACKGROUND: The Mediterranean diet (MeDi) is known to prevent cardiovascular events but the mechanisms mediating this association are not fully understood. OBJECTIVE: The objective of the study was to examine the association between MeDi adherence and the presence and extent of atherosclerotic plaques in carotid, femoral, and aorta territories and its relationship with risk factors in asymptomatic middle-aged adults. METHODS: Cross-sectional analysis of the Aragon Workers' Health Study, a cohort of 2588 subjects (94.9% men aged 51.3 ± 3.89 years) without previous cardiovascular history. Participants underwent carotid, femoral, and aorta ultrasound for the quantification of number and thickness of plaques and intima-media thickness. To estimate the participant's adherence to MeDi, we computed the Alternative MEDiterranean index (aMED). RESULTS: The overall aMED score was 4.19 ± 1.70, representing a moderate adherence to MeDi. aMED score was associated with the presence of plaque in femoral arteries (odds ratio highest vs lowest aMED score quartile: 0.63; 95% confidence interval: 0.48-0.83; P trend = .045) independently of risk factors and mediators. The strongest association between aMED quartiles and presence of plaque was found among smokers, both in femoral (0.39 [0.22-0.69]; P trend = .001) and in any territory (0.33 [0.14-0.79], P trend = .008). aMED was inversely associated with the number of plaques in all territories except for carotids. CONCLUSION: MeDi adherence showed a dose-dependent protective association with the presence, number, and thickness of plaques independent of other risk factors. The association was strongest for femoral arteries and among smokers.


Assuntos
Aterosclerose/dietoterapia , Doenças das Artérias Carótidas/dietoterapia , Dieta Mediterrânea , Placa Aterosclerótica/dietoterapia , Aterosclerose/epidemiologia , Aterosclerose/fisiopatologia , Aterosclerose/prevenção & controle , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/prevenção & controle , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/fisiopatologia , Placa Aterosclerótica/prevenção & controle , Fatores de Risco
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