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1.
J Cardiovasc Magn Reson ; 22(1): 68, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32938483

RESUMO

BACKGROUND: Cardiovascular magnetic resonance (CMR) phase contrast (PC) flow measurements suffer from phase offset errors. Background subtraction based on stationary phantom measurements can most reliably be used to overcome this inaccuracy. Stationary tissue correction is an alternative and does not require additional phantom scanning. The aim of this study was 1) to compare measurements with and without stationary tissue correction to phantom corrected measurements on different GE Healthcare CMR scanners using different software packages and 2) to evaluate the clinical implications of these methods. METHODS: CMR PC imaging of both the aortic and pulmonary artery flow was performed in patients on three different 1.5 T CMR scanners (GE Healthcare) using identical scan parameters. Uncorrected, first, second and third order stationary tissue corrected flow measurement were compared to phantom corrected flow measurements, our reference method, using Medis QFlow, Circle cvi42 and MASS software. The optimal (optimized) stationary tissue order was determined per scanner and software program. Velocity offsets, net flow, clinically significant difference (deviation > 10% net flow), and regurgitation severity were assessed. RESULTS: Data from 175 patients (28 (17-38) years) were included, of which 84% had congenital heart disease. First, second and third order and optimized stationary tissue correction did not improve the velocity offsets and net flow measurements. Uncorrected measurements resulted in the least clinically significant differences in net flow compared to phantom corrected data. Optimized stationary tissue correction per scanner and software program resulted in net flow differences (> 10%) in 19% (MASS) and 30% (Circle cvi42) of all measurements compared to 18% (MASS) and 23% (Circle cvi42) with no correction. Compared to phantom correction, regurgitation reclassification was the least common using uncorrected data. One CMR scanner performed worse and significant net flow differences of > 10% were present both with and without stationary tissue correction in more than 30% of all measurements. CONCLUSION: Phase offset errors had a significant impact on net flow quantification, regurgitation assessment and varied greatly between CMR scanners. Background phase correction using stationary tissue correction worsened accuracy compared to no correction on three GE Healthcare CMR scanners. Therefore, careful assessment of phase offset errors at each individual scanner is essential to determine whether routine use of phantom correction is necessary. TRIAL REGISTRATION: Observational Study.


Assuntos
Aorta/diagnóstico por imagem , Insuficiência da Valva Aórtica/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Hemodinâmica , Interpretação de Imagem Assistida por Computador , Imagem Cinética por Ressonância Magnética/instrumentação , Artéria Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Aorta/fisiopatologia , Insuficiência da Valva Aórtica/fisiopatologia , Velocidade do Fluxo Sanguíneo , Criança , Feminino , Cardiopatias Congênitas/fisiopatologia , Humanos , Masculino , Imagens de Fantasmas , Valor Preditivo dos Testes , Artéria Pulmonar/fisiopatologia , Insuficiência da Valva Pulmonar/fisiopatologia , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
2.
PLoS One ; 15(8): e0238112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857805

RESUMO

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE-/- mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. All in vivo MR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE-/- mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.


Assuntos
Aorta/diagnóstico por imagem , Imagem por Ressonância Magnética , Placa Aterosclerótica/diagnóstico por imagem , Animais , Aorta/patologia , Aorta/fisiopatologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Peso Corporal , Dieta Ocidental , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Estudos Longitudinais , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Camundongos Knockout , Placa Aterosclerótica/patologia , Placa Aterosclerótica/fisiopatologia , Distribuição Aleatória , Fluxo Sanguíneo Regional , Estresse Mecânico
3.
High Blood Press Cardiovasc Prev ; 27(4): 299-308, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32572706

RESUMO

Large conductive arteries undergo to structural modifications by aging, eventually leading to increased vascular stiffness. As consequence, cardiovascular hemodynamic changes by increasing central blood pressure which may be also associated to the remodelling of peripheral resistance arteries that contribute to increase further the central vascular stiffness and blood pressure. These modifications resemble the ones that has been shown in essential hypertension, thus a condition of "early vascular aging" has been described in hypertensive patients. Since hypertension related target organs, particularly the heart, face aortic blood pressure rather than brachial blood pressure, it has been recently suggested that central blood pressure and other parameters of large arteries' stiffness, including pulse wave velocity (PWV), may better correlate with subclinical organ damage and might be useful to assess the cardiovascular risk of patients beyond the traditional risk factors. Different devices have been validated to measure central blood pressure and PWV, and are currently available for clinical use. The increasing application of these tools in clinical practice could improve the management of hypertensive patients by better defining the cardiovascular risk and address the antihypertensive therapy.


Assuntos
Envelhecimento , Aorta/fisiopatologia , Pressão Arterial , Hipertensão/fisiopatologia , Remodelação Vascular , Rigidez Vascular , Fatores Etários , Animais , Anti-Hipertensivos/uso terapêutico , Aorta/efeitos dos fármacos , Pressão Arterial/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Remodelação Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos
5.
Toxicol Appl Pharmacol ; 400: 115041, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428593

RESUMO

Respiratory ailments have plagued occupational and public health communities exposed to World Trade Center (WTC) dust since the September 11, 2001 attack on the Twin Towers in Lower Manhattan. We proposed that these ailments were proposed to be induced by inhalation exposure to WTC particulate matter (WTCPM), that was released during the collapse of the buildings and its subsequent resuspension during cleanup. We investigated this hypothesis using both an in vitro and an in vivo mouse intranasal (IN) exposure models to identify the inflammatory potential of WTCPM with specific emphasis on respiratory and endothelial tissue responses. The in vitro exposure studies found WTCPM exposure to be positively correlated with cytotoxicity and increased NO2- production in both BEAS-2B pulmonary epithelial cells and THP-1 macrophage cells. The in vivo C57BL/6 mouse studies found significant increases in inflammatory markers including increases in polymorphonuclear neutrophil (PMN) influx into nasal and bronchoalveolar lavage fluids (NLF and BALF), as well as increased levels of total protein and cytokine/chemokines levels. Concurrently, NLF, BALF, and serum NO2- levels exhibited significant homeostatic temporal deviations as well as temporal myograohic aortic dysfunction in myography studies. Respiratory exposure to- and evidence -based retention of- WTCPM may have contributed to chronic systemic effects in exposed mice that r resembled to observed effects in WTCPM-exposed human populations. Collectively, these findings are reflective of WTCPM exposure and its effect(s) on respiratory and aortic tissues, highlighting potential dysfunctional pathways that may precipitate inflammatory events, while simultaneously altering homeostatic balances. The tight interplay between these balances, when chronically altered, may contribute to- or result in- chronically diseased pathological states.


Assuntos
Poluentes Atmosféricos/toxicidade , Materiais de Construção/toxicidade , Poeira/análise , Endotélio Vascular/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Pneumonia/induzido quimicamente , Poluentes Atmosféricos/análise , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Materiais de Construção/análise , Endotélio Vascular/fisiopatologia , Humanos , Exposição por Inalação/análise , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/imunologia , Cidade de Nova Iorque , Ataques Terroristas de 11 de Setembro , Células THP-1
6.
Arterioscler Thromb Vasc Biol ; 40(6): 1510-1522, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32349535

RESUMO

OBJECTIVE: Endothelial Cav-1 (caveolin-1) expression plays a relevant role during atherogenesis by controlling NO production, vascular inflammation, LDL (low-density lipoprotein) transcytosis, and extracellular matrix remodeling. Additional studies have identified cholesterol-rich membrane domains as important regulators of autophagy by recruiting ATGs (autophagy-related proteins) to the plasma membrane. Here, we investigate how the expression of Cav-1 in the aortic endothelium influences autophagy and whether enhanced autophagy contributes to the atheroprotective phenotype observed in Cav-1-deficient mice. Approach and Results: To analyze the impact of Cav-1 deficiency on regulation of autophagy in the aortic endothelium during the progression of atherosclerosis, we fed Ldlr-/- and Cav-1-/-Ldlr-/- mice a Western diet and assessed autophagy in the vasculature. We observe that the absence of Cav-1 promotes autophagy activation in athero-prone areas of the aortic endothelium by enhancing autophagic flux. Mechanistically, we found that Cav-1 interacts with the ATG5-ATG12 complex and influences the cellular localization of autophagosome components in lipid rafts, which controls the autophagosome formation and autophagic flux. Pharmacological inhibition of autophagy attenuates the atheroprotection observed in Cav-1-/- mice by increasing endothelial inflammation and macrophage recruitment, identifying a novel molecular mechanism by which Cav-1 deficiency protects against the progression of atherosclerosis. CONCLUSIONS: These results identify Cav-1 as a relevant regulator of autophagy in the aortic endothelium and demonstrate that pharmacological suppression of autophagic flux in Cav-1-deficient mice attenuates the atheroprotection observed in Cav-1-/- mice. Additionally, these findings suggest that activation of endothelial autophagy by blocking Cav-1 might provide a potential therapeutic strategy for cardiovascular diseases including atherosclerosis.


Assuntos
Aterosclerose/prevenção & controle , Autofagia/fisiologia , Caveolina 1/deficiência , Endotélio Vascular/fisiopatologia , Vasculite/prevenção & controle , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Aorta/patologia , Aorta/fisiopatologia , Aorta/ultraestrutura , Aterosclerose/etiologia , Autofagia/efeitos dos fármacos , Caveolina 1/análise , Caveolina 1/fisiologia , Dieta Ocidental , Células Endoteliais/química , Células Endoteliais/fisiologia , Células Endoteliais/ultraestrutura , Endotélio Vascular/química , Endotélio Vascular/ultraestrutura , Feminino , Humanos , Masculino , Microdomínios da Membrana/química , Microdomínios da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Receptores de LDL/deficiência
7.
Am J Physiol Heart Circ Physiol ; 319(1): H51-H65, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412791

RESUMO

Although there is a strong association between cigarette smoking exposure (CSE) and vascular endothelial dysfunction (VED), the underlying mechanisms by which CSE triggers VED remain unclear. Therefore, studies were performed to define these mechanisms using a chronic mouse model of cigarette smoking (CS)-induced cardiovascular disease mirroring that in humans. C57BL/6 male mice were subjected to CSE for up to 48 wk. CSE impaired acetylcholine (ACh)-induced relaxation of aortic and mesenteric segments and triggered hypertension, with mean arterial blood pressure at 32 and 48 wk of exposure of 122 ± 6 and 135 ± 5 mmHg compared with 99 ± 4 and 102 ± 6 mmHg, respectively, in air-exposed mice. CSE led to monocyte activation with superoxide generation in blood exiting the pulmonary circulation. Macrophage infiltration with concomitant increase in NADPH oxidase subunits p22phox and gp91phox was seen in aortas of CS-exposed mice at 16 wk, with further increase out to 48 wk. Associated with this, increased superoxide production was detected that decreased with Nox inhibition. Tetrahydrobiopterin was progressively depleted in CS-exposed mice but not in air-exposed controls, resulting in endothelial nitric oxide synthase (eNOS) uncoupling and secondary superoxide generation. CSE led to a time-dependent decrease in eNOS and Akt expression and phosphorylation. Overall, CSE induces vascular monocyte infiltration with increased NADPH oxidase-mediated reactive oxygen species generation and depletes the eNOS cofactor tetrahydrobiopterin, uncoupling eNOS and triggering a vicious cycle of oxidative stress with VED and hypertension. Our study provides important insights toward understanding the process by which smoking contributes to the genesis of cardiovascular disease and identifies biomarkers predictive of disease.NEW & NOTEWORTHY In a chronic model of smoking-induced cardiovascular disease, we define underlying mechanisms of smoking-induced vascular endothelial dysfunction (VED). Smoking exposure triggered VED and hypertension and led to vascular macrophage infiltration with concomitant increase in superoxide and NADPH oxidase levels as early as 16 wk of exposure. This oxidative stress was accompanied by tetrahydrobiopterin depletion, resulting in endothelial nitric oxide synthase uncoupling with further superoxide generation triggering a vicious cycle of oxidative stress and VED.


Assuntos
Endotélio Vascular/metabolismo , Leucócitos/metabolismo , Estresse Oxidativo , Lesão por Inalação de Fumaça/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Vasodilatação , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Pressão Sanguínea , Endotélio Vascular/fisiopatologia , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lesão por Inalação de Fumaça/etiologia , Lesão por Inalação de Fumaça/fisiopatologia , Superóxidos/metabolismo
8.
Arterioscler Thromb Vasc Biol ; 40(7): e203-e213, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460580

RESUMO

OBJECTIVE: Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFß [transforming growth factor-beta]-activated kinase 1) is a mediator of noncanonical TGFß signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation. Approach and Results: In both human and mouse AVF, immunoreactivity of TAK1, JNK (c-Jun N-terminal kinase), p38, collagen 1, and fibronectin was significantly increased compared with control veins. Manipulation of TAK1 in vivo altered AVF wall thickening and luminal diameter; reduced TAK1 function was associated with reduced thickness and smaller diameter, whereas activation of TAK1 function was associated with increased thickness and larger diameter. Arterial magnitudes of laminar shear stress (20 dyne/cm2) activated noncanonical TGFß signaling including TAK1 phosphorylation in mouse endothelial cells. CONCLUSIONS: TAK1 is increased in AVF, and TAK1 manipulation in a mouse AVF model regulates AVF thickness and diameter. Targeting noncanonical TGFß signaling such as TAK1 might be a novel therapeutic approach to improve AVF maturation.


Assuntos
Aorta/cirurgia , Derivação Arteriovenosa Cirúrgica , MAP Quinase Quinase Quinases/metabolismo , Grau de Desobstrução Vascular , Remodelação Vascular , Veia Cava Inferior/cirurgia , Animais , Aorta/diagnóstico por imagem , Aorta/enzimologia , Aorta/fisiopatologia , Células Cultivadas , Colágeno Tipo I/metabolismo , Células Endoteliais/enzimologia , Fibronectinas/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , MAP Quinase Quinase Quinases/genética , Masculino , Mecanotransdução Celular , Camundongos Endogâmicos C57BL , Fosforilação , Estresse Mecânico , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/enzimologia , Veia Cava Inferior/fisiopatologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-32357115

RESUMO

Type 2 diabetic (T2DM) coronary resistance microvessels (CRMs) undergo inward hypertrophic remodeling associated with reduced stiffness and reduced coronary blood flow in both mice and pig models. Since reduced stiffness does not appear to be due to functional changes in the extracellular matrix, this study tested the hypothesis that decreased CRM stiffness in T2DM is due to reduced vascular smooth muscle cell (VSMC) stiffness, which impacts the traction force generated by VSMCs. Atomic force microscopy (AFM) and traction force microscopy (TFM) were conducted on primary low-passage CRM VSMCs from normal Db/db and T2DM db/db mice in addition to low-passage normal and T2DM deidentified human coronary VSMCs. Elastic modulus was reduced in T2DM mouse and human coronary VSMCs compared with normal (mouse: Db/db 6.84 ± 0.34 kPa vs. db/db 4.70 ± 0.19 kPa, P < 0.0001; human: normal 3.59 ± 0.38 kPa vs. T2DM 2.61 ± 0.35 kPa, P = 0.05). Both mouse and human T2DM coronary microvascular VSMCs were less adhesive to fibronectin compared with normal. T2DM db/db coronary VSMCs generated enhanced traction force by TFM (control 692 ± 67 Pa vs. db/db 1,507 ± 207 Pa; P < 0.01). Immunoblot analysis showed that T2DM human coronary VSMCs expressed reduced ß1-integrin and elevated ß3-integrin (control 1.00 ± 0.06 vs. T2DM 0.62 ± 0.14, P < 0.05 and control 1.00 ± 0.49 vs. T2DM 3.39 ± 1.05, P = 0.06, respectively). These data show that T2DM coronary VSMCs are less stiff and less adhesive to fibronectin but are able to generate enhanced force, corroborating previously published computational findings that decreasing cellular stiffness increases the cells' ability to generate higher traction force.NEW & NOTEWORTHY We show here that a potential causative factor for reduced diabetic coronary microvascular stiffness is the direct reduction in coronary vascular smooth muscle cell stiffness. These cells were also able to generate enhanced traction force, validating previously published computational models. Collectively, these data show that smooth muscle cell stiffness can be a contributor to overall tissue stiffness in the coronary microcirculation, and this may be a novel area of interest for therapeutic targets.


Assuntos
Aorta/fisiopatologia , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Adulto , Animais , Módulo de Elasticidade , Feminino , Humanos , Masculino , Camundongos , Microcirculação/fisiologia , Microscopia de Força Atômica , Pessoa de Meia-Idade , Miócitos de Músculo Liso/fisiologia
10.
J Surg Res ; 252: 255-263, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32304932

RESUMO

BACKGROUND: The impact of race and gender on surgical outcomes has been studied in infrainguinal revascularization for peripheral arterial disease. The aim of this study is to explore how race and gender affect the outcomes of suprainguinal bypass (SIB) for aortoiliac occlusive disease. MATERIALS AND METHODS: Patients who underwent SIB were identified from the procedure-targeted National Surgical Quality Improvement Program data set (2011-2016). Patients were stratified into four groups: nonblack males, black males (BM), nonblack females, and black females (BF). Primary outcomes were 30-d major adverse cardiac events, a composite of myocardial infarction, stroke, or death; postoperative bleeding requiring transfusion or intervention; major amputation and prolonged length of stay (>10 d). Predictors of outcomes were determined by multivariable logistic regression analysis. RESULTS: About 5044 patients were identified. BM were younger, more likely to be smokers, less likely to be on antiplatelet drug or statin, and to receive elective SIB (all P ≤ 0.01). BFs were more likely to be diabetic and functionally dependent (all P ≤ 0.02). Major adverse cardiac events were not significantly different among all groups. BM had a threefold higher risk of amputation (adjusted odds ratio [OR] [95% confidence interval (95% CI)], 3.10 [1.50-6.43]; P < 0.002). Female gender was associated with bleeding in both races, that association was more drastic in BF (OR [95% CI], 2.43 [1.63-3.60]; P < 0.0001), whereas nonblack females (OR [95% CI], 1.46 [1.19-1.80]; P < 0.0001). BF had higher odds of prolonged length of stay (OR [95% CI]: 1.62 [1.08-2.42]; P < 0.019). CONCLUSIONS: In this large retrospective study, we demonstrated the racial and gender disparity in SIB outcomes. BM had more than threefold increase in amputation risk as compared with nonblack males. Severe bleeding risk was more than doubled in BF. Race and gender consideration is warranted in risk assessment when patients are selected for aortoiliac disease revascularization, which in turn necessitate preoperative risk modification and optimization in addition to enhancing their access to primary preventive care measures.


Assuntos
Procedimentos Endovasculares/efeitos adversos , Disparidades nos Níveis de Saúde , Síndrome de Leriche/cirurgia , Infarto do Miocárdio/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Afro-Americanos/estatística & dados numéricos , Fatores Etários , Idoso , Amputação/estatística & dados numéricos , Aorta/fisiopatologia , Aorta/cirurgia , Procedimentos Endovasculares/métodos , Feminino , Mortalidade Hospitalar , Humanos , Artéria Ilíaca/fisiopatologia , Artéria Ilíaca/cirurgia , Síndrome de Leriche/complicações , Síndrome de Leriche/mortalidade , Síndrome de Leriche/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
11.
Nutr Metab Cardiovasc Dis ; 30(5): 843-846, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32278610

RESUMO

BACKGROUND AND AIMS: Prospective epidemiological studies highlighted recently the link between artificial sweeteners (AS) consumption and the risk of developing cardiometabolic diseases. However, underlying mechanisms remain unknown. Thus, the aim of this preliminary study was to characterize, in a healthy rat population, the effect of chronic AS consumption on body composition and vascular function, an early marker for cardiovascular disease. METHODS AND RESULTS: Healthy Wistar rats followed a 10-week standard diet including the consumption of water sweetened or not with a sucralose/acesulfame potassium solution at different concentrations: for moderate consumption at 1 and 2 mg.kg-1.day-1, respectively or high intake at 15 and 15 mg.kg-1.day-1 for both molecules (acceptable daily intake). Body fat composition has been evaluated and ex vivo aortic vasomotor function has been investigated with a pharmacological approach. CONCLUSION: Both groups of AS-treated rats showed a significant increase in subcutaneous and perirenal adipose tissue mass storage, without changes in total body mass. However, rats that have consumed AS at Acceptable Daily Intake (ADI) concentration revealed a significant vascular endothelial dysfunction compared to other groups. These results are interesting because they will help to better explain the observed increase in cardiometabolic risk.


Assuntos
Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Sacarose/análogos & derivados , Edulcorantes/toxicidade , Tiazinas/toxicidade , Vasodilatação/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Aorta/fisiopatologia , Relação Dose-Resposta a Droga , Endotélio Vascular/fisiopatologia , Dados Preliminares , Ratos Wistar , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/fisiopatologia , Sacarose/administração & dosagem , Sacarose/toxicidade , Edulcorantes/administração & dosagem , Tiazinas/administração & dosagem
12.
Cardiovasc Eng Technol ; 11(3): 283-294, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32314124

RESUMO

PURPOSE: Optimal assessment of cardiovascular performance requires simultaneous measurement of load independent left ventricular (LV) contractility, arterial function and LV/arterial coupling. We aimed to demonstrate feasibility of non-invasive ventricular pressure-volume and aortic pressure-flow-impedance measurements using simultaneous arterial tonometry (AT) and cardiovascular magnetic resonance imaging (CMRI). METHODS: 21 consecutive patients referred for CMRI were enrolled to undergo a simultaneous AT and CMRI protocol. A CMRI compatible AT apparatus provided aortic end-systolic pressure, taken to be equivalent to LV end-systolic pressure in the absence of aortic stenosis. CMRI provided LV volume and aortic flow at the time of pressure acquisition. Pressure-volume relationships were determined and correlated to traditional parameters of LV function including ejection fraction and circumferential strain. Aortic pressure-flow relationships were used to determine aortic characteristic impedance and systemic vascular resistance. RESULTS: Simultaneous AT and CMRI permitted measurement of LV end-systolic elastance, preload recruitable stroke work, arterial elastance, aortic characteristic impedance and systemic vascular resistance. Absolute values were within the expected range for our cohort, were highly reproducible and showed appropriately directed correlation to traditional parameters. CONCLUSION: Non-invasive assessment of LV pressure-volume and aortic pressure-flow relationships are both feasible and reproducible using simultaneous AT and CMRI. Methods permit assessment of load independent LV contractility, arterial function and LV/arterial coupling from a single non-invasive diagnostic encounter.


Assuntos
Aorta/diagnóstico por imagem , Artéria Braquial/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Hemodinâmica , Imagem por Ressonância Magnética , Manometria , Contração Miocárdica , Rigidez Vascular , Função Ventricular Esquerda , Adolescente , Adulto , Fatores Etários , Idoso , Aorta/fisiopatologia , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Elasticidade , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-32302491

RESUMO

Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models of experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP and vascular dysfunction in a 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8-12 wk) were randomly assigned, and fed a 0.1% or 4.0% NaCl diet, and instrumented with telemetry units to measure ABP. Then, the 2K1C model was produced by placing a cuff around the right renal artery. Systolic, diastolic, and mean ABP were significantly higher in mice fed 4.0% vs. 0.1% NaCl at 1 wk but not after 3 wk. Interestingly, 2K1C hypertension progressively increased arterial pulse pressure in both groups; however, the magnitude was significantly greater in mice fed 4.0% vs. 0.1% NaCl at 3 wk. Moreover, pulse wave velocity was significantly greater in 2K1C mice fed 4.0% vs. 0.1% NaCl diet or sham-operated mice fed either diet. Histological assessment of aortas indicated no structural differences among groups. Finally, endothelium-dependent vasodilation was significantly and selectively attenuated in the aorta but not mesenteric arteries of 2K1C mice fed 4.0% NaCl vs. 0.1% NaCl or sham-operated control mice. The findings suggest that dietary salt loading transiently exaggerates 2K1C renovascular hypertension but promotes chronic aortic stiffness and selective aortic vascular dysfunction.NEW & NOTEWORTHY High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness.


Assuntos
Hipertensão Renovascular/etiologia , Cloreto de Sódio na Dieta/efeitos adversos , Rigidez Vascular , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/fisiopatologia , Pressão Sanguínea , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cloreto de Sódio na Dieta/toxicidade , Vasoconstrição
14.
Int J Cardiovasc Imaging ; 36(8): 1429-1436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32303878

RESUMO

The ascending aorta dilatation in the bicuspid aortic valve (BAV) patients is often attributed to congenital abnormalities of the aortic wall, but it may be related to hemodynamic disturbances in the course of BAV disease. At present, ascending aortic diameter is used as almost sole but weak predictor of aortic dissection and rupture in BAV. We examined the association between aortic wall mechanics and severity of aortic valve disease including different cusps fusion patterns using conventional echocardiography and tissue Doppler imaging (TDI). We prospectively studied 106 BAV patients: 72 with right-left (R-L) coronary cusp fusion were matched 1:1 to 34 patients with right-noncoronary (R-N) cusp fusion obtaining 34 pairs of patients. Peak systolic radial velocity and acceleration of the ascending aortic wall, measured by TDI, were used as an index of hemodynamic stress imposed on the aorta. Paired analysis showed higher aortic wall radial velocity (4.71 ± 1.61 cm/s vs. 3.33 ± 1.44 cm/s, p = 0.001) and acceleration (1.08 ± 0.46 m/s2 vs. 0.80 ± 0.34 m/s2, p = 0.015) in-R-L compared to R-N fusion. Pearson correlation showed association of ascending tubular aortic diameter with age (r = 0.258, p = 0.012), weight (r = 0.323, p = 0.001), peak aortic valve gradient (r = 0.386, p = 0.0001), aortic root diameter (r = 0.439, p < 0.0001), and R-N fusion pattern (r = 0.209, p = 0.043). Aortic root diameter was related to male gender (r = 0.296, p = 0.003), weight (r = 0.381, p = 0.0001), ascending aortic diameter (r = 0.439, p < 0.0001), and severity of aortic regurgitation (r = 0.337, p = 0.0009). Regional differences in aortic wall motion between different BAV cusp fusion patterns and association of aortic diameters with the severity of aortic valve disease, both suggest a deleterious hemodynamic impact of cusp fusion patterns and aortic valve dysfunction on ascending aortic wall. Assessment of aortic hemodynamic by TDI is feasible and could be potentially used to improve prediction of acute aortic complications, thus helping to establish optimal timing of aortic surgery in BAV patients.


Assuntos
Aorta/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Valva Aórtica/anormalidades , Ecocardiografia Doppler em Cores , Doenças das Valvas Cardíacas/diagnóstico por imagem , Hemodinâmica , Adulto , Aorta/fisiopatologia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/fisiopatologia , Fenômenos Biomecânicos , Dilatação Patológica , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
15.
Int J Cardiovasc Imaging ; 36(8): 1533-1542, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32314122

RESUMO

Aortic diameter measurements play a crucial role for the indication of aortic root surgery in Marfan patients. However, for magnetic resonance angiography (MRA)-derived measurements, there is no consensus on whether the aortic wall should be included or excluded in the aortic diameter. The purpose of this retrospective study was to compare the reliability of non-contrast bright blood MRA aortic inner-to-inner and outer-to-outer edge measurements in patients with Marfan syndrome. Forty Marfan patients underwent ECG-gated balanced steady-state free-precession MRA of the aorta at 1.5 T. Two readers independently performed inner and outer measurements at different aortic levels. They rated the image quality of the delineation of both inner and outer vessel wall edges on a four-point scale. MRA-derived diameters of the sinuses of Valsalva were compared with echocardiography-derived diameters. Aortic vessel wall delineation score was rated higher at all levels for inner than for outer vessel walls (p < 0.001). Inter- and intraobserver variances of aortic measurements were smaller for inner-to-inner measurements at the sinuses of Valsalva, sinotubular junction and ascending aorta (p < 0.03). There was a difference of 1.1 ± 2.3 mm for inner MRA measurements (p = 0.014) and 6.9 ± 3.1 mm for outer MRA measurements (p < 0.001) when compared to echocardiographic leading-edge measurements. Inner-to-inner vessel wall diameter measurements in non-contrast bright blood MRA provide more reliable diameters when compared to outer-to-outer vessel wall measurements of the aortic root. Therefore, we propose to rely on inner rather than outer aortic wall measurements in non-contrast-MRA when monitoring aortic diameters in patients with Marfan syndrome.


Assuntos
Aorta/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Angiografia por Ressonância Magnética , Síndrome de Marfan/complicações , Seio Aórtico/diagnóstico por imagem , Adolescente , Adulto , Aorta/fisiopatologia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/fisiopatologia , Técnicas de Imagem de Sincronização Cardíaca , Dilatação Patológica , Eletrocardiografia , Feminino , Humanos , Masculino , Síndrome de Marfan/diagnóstico , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Seio Aórtico/fisiopatologia , Remodelação Vascular , Adulto Jovem
16.
Arterioscler Thromb Vasc Biol ; 40(6): 1574-1586, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295423

RESUMO

OBJECTIVE: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.


Assuntos
Artérias/fisiopatologia , Arteriosclerose/fisiopatologia , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Envelhecimento , Aorta/fisiopatologia , Pressão Arterial , Pressão Sanguínea , Extremidades/irrigação sanguínea , Feminino , Humanos , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , África do Sul , Acidente Vascular Cerebral/fisiopatologia , Rigidez Vascular
17.
Am J Physiol Renal Physiol ; 318(5): F1220-F1228, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32281419

RESUMO

Consumption of a Western diet (WD) induces central aortic stiffening that contributes to the transmittance of pulsatile blood flow to end organs, including the kidney. Our recent work supports that endothelial epithelial Na+ channel (EnNaC) expression and activation enhances aortic endothelial cell stiffening through reductions in endothelial nitric oxide (NO) synthase (eNOS) and bioavailable NO that result in inflammatory and oxidant responses and perivascular fibrosis. However, the role that EnNaC activation has on endothelial responses in the renal circulation remains unknown. We hypothesized that cell-specific deletion of the α-subunit of EnNaC would prevent WD-induced central aortic stiffness and protect the kidney from endothelial dysfunction and vascular stiffening. Twenty-eight-week-old female αEnNaC knockout and wild-type mice were fed either mouse chow or WD containing excess fat (46%), sucrose, and fructose (17.5% each). WD feeding increased fat mass, indexes of vascular stiffening in the aorta and renal artery (in vivo pulse wave velocity and ultrasound), and renal endothelial cell stiffening (ex vivo atomic force microscopy). WD further impaired aortic endothelium-dependent relaxation and renal artery compliance (pressure myography) without changes in blood pressure. WD-induced renal arterial stiffening occurred in parallel to attenuated eNOS activation, increased oxidative stress, and aortic and renal perivascular fibrosis. αEnNaC deletion prevented these abnormalities and support a novel mechanism by which WD contributes to renal arterial stiffening that is endothelium and Na+ channel dependent. These results demonstrate that cell-specific EnNaC is important in propagating pulsatility into the renal circulation, generating oxidant stress, reduced bioavailable NO, and renal vessel wall fibrosis and stiffening.


Assuntos
Aorta/metabolismo , Dieta Ocidental/efeitos adversos , Canais Epiteliais de Sódio/metabolismo , Artéria Renal/fisiopatologia , Doenças Vasculares/metabolismo , Rigidez Vascular , Animais , Aorta/patologia , Aorta/fisiopatologia , Elasticidade , Canais Epiteliais de Sódio/deficiência , Canais Epiteliais de Sódio/genética , Feminino , Fibrose , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Artéria Renal/patologia , Transdução de Sinais , Doenças Vasculares/genética , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologia , Remodelação Vascular
20.
Clin Imaging ; 63: 16-23, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32120308

RESUMO

OBJECTIVES: Pulmonary hypertension (PH) is a progressive, potentially fatal disease, difficult to diagnose early due to non-specific nature of symptoms. PH is associated with increased morbidity and death in many respiratory and cardiac disorders, and with all-cause mortality, independent of age and cardiopulmonary disease. The main pulmonary artery diameter (MPA), and ratio of MPA to adjacent ascending aorta (AA), MPA:AA, on Chest CT are strong indicators of suspected PH. Our goal was to determine the prevalence of abnormally high values of these indicators of PH in asymptomatic low-dose CT (LDCT) screening participants at risk of lung cancer, and determine the associated risk factors. METHODS: We reviewed consecutive baseline LDCT scans of 1949 smokers in an IRB-approved study. We measured the MPA and AA diameter and calculated MPA:AA ratio. We defined abnormally high values as being more than two standard deviations above the average (MPA ≥ 34 mm and MPA:AA ≥ 1.0). Regression analyses were used to identify risk factors and CT findings of participants associated with high values. RESULTS: The prevalence of MPA ≥ 34 mm and MPA:AA ≥ 1.0 was 4.2% and 6.9%, respectively. Multivariable regression demonstrated that BMI was a significant risk factor, both for MPA ≥ 34 mm (OR = 1.07, p < 0.0001) and MPA:AA ≥ 1.0 (OR = 1.04, p = 0.003). Emphysema was significant in the univariate but not in the multivariate analysis. CONCLUSIONS: We determined that the possible prevalence of PH as defined by abnormally high values of MPA and of MPA:AA was greater than previously described in the general population and that pulmonary consultation be recommended for these participants, in view of the significance of PH.


Assuntos
Aorta/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Adulto , Aorta/anatomia & histologia , Aorta/fisiopatologia , Detecção Precoce de Câncer , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Pulmão/fisiopatologia , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/anatomia & histologia , Artéria Pulmonar/fisiopatologia , Fatores de Risco , Fumantes , Tomografia Computadorizada por Raios X
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