RESUMEN
In addition to genetic and epigenetic inheritance, somatic variation may contribute to cardiovascular disease (CVD) risk. CVD-associated somatic mutations have been reported in human clonal hematopoiesis, but evidence in the atheroma is lacking. To probe for somatic variation in atherosclerosis, we sought single-nucleotide private variants (PVs) in whole-exome sequencing (WES) data of aorta, liver, and skeletal muscle of two C57BL/6J coisogenic male ApoE null/wild-type (WT) sibling pairs, and RNA-seq data of one of the two pairs. Relative to the C57BL/6 reference genome, we identified 9 and 11 ApoE null aorta- and liver-specific PVs that were shared by all WES and RNA-seq datasets. Corresponding PVs in WT sibling aorta and liver were 1 and 0, respectively, and not overlapping with ApoE null PVs. Pyrosequencing analysis of 4 representative PVs in 17 ApoE null aortas and livers confirmed tissue-specific shifts toward the alternative allele, in addition to significant deviations from mendelian allele ratios. Notably, all aorta and liver PVs were present in the dbSNP database and were predominantly transition mutations within atherosclerosis-related genes. The majority of PVs were in discrete clusters approximately 3 Mb and 65 to 73 Mb away from hypermutable immunoglobin loci in chromosome 6. These features were largely shared with previously reported CVD-associated somatic mutations in human clonal hematopoiesis. The observation that SNPs exhibit tissue-specific somatic DNA mosaicism in ApoE null mice is potentially relevant for genetic association study design. The proximity of PVs to hypermutable loci suggests testable mechanistic hypotheses.
Asunto(s)
Enfermedades de la Aorta/genética , Aterosclerosis/genética , Mosaicismo , Polimorfismo de Nucleótido Simple , Animales , Aorta/patología , Enfermedades de la Aorta/patología , Aterosclerosis/patología , Bases de Datos Genéticas , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Fenotipo , RNA-Seq , Secuenciación del ExomaRESUMEN
A healthy dietary pattern and high quality nutrient intake reduce atherosclerotic cardiovascular disease risk. Red wine grape pomace (RWGP)-a rich natural source of dietary fiber and antioxidants-appears to be a potential functional food ingredient. The impact of a dietary supplementation with RWGP flour was evaluated in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice, a model of lethal ischemic heart disease. SR-B1 KO/ApoER61h/h mice were fed with atherogenic (high fat, cholesterol, and cholic acid, HFC) diet supplemented with: (a) 20% chow (HFC-Control), (b) 20% RWGP flour (HFC-RWGP), or (c) 10% chow/10% oat fiber (HFC-Fiber); and survival time was evaluated. In addition, SR-B1 KO/ApoER61h/h mice were fed for 7 or 14 days with HFC-Control or HFC-RWGP diets and plasma lipid levels, inflammation, oxidative damage, and antioxidant activity were measured. Atherosclerosis and myocardial damage were assessed by histology and magnetic resonance imaging, respectively. Supplementation with RWGP reduced premature death, changed TNF-α and IL-10 levels, and increased plasma antioxidant activity. Moreover, decreased atheromatous aortic and brachiocephalic plaque sizes and attenuated myocardial infarction and dysfunction were also observed. These results suggest that RWGP flour intake may be used as a non-pharmacological therapeutic approach, contributing to decreased progression of atherosclerosis, reduced coronary heart disease, and improved cardiovascular outcomes.
Asunto(s)
Antioxidantes/administración & dosificación , Aorta/metabolismo , Enfermedades de la Aorta/prevención & control , Aterosclerosis/prevención & control , Suplementos Dietéticos , Frutas/química , Isquemia Miocárdica/prevención & control , Miocardio/metabolismo , Estrés Oxidativo , Extractos Vegetales/administración & dosificación , Vitis/química , Alimentación Animal , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Aorta/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/genética , Aterosclerosis/patología , Biomarcadores/sangre , Dieta Aterogénica , Modelos Animales de Enfermedad , Femenino , Mediadores de Inflamación/sangre , Interleucina-10/sangre , Lípidos/sangre , Masculino , Ratones Noqueados para ApoE , Isquemia Miocárdica/sangre , Isquemia Miocárdica/genética , Isquemia Miocárdica/patología , Miocardio/patología , Extractos Vegetales/sangre , Extractos Vegetales/aislamiento & purificación , Placa Aterosclerótica , Receptores Depuradores de Clase B/deficiencia , Receptores Depuradores de Clase B/genética , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Aims: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine (Ala1-angiotensin-(1-7)) is a new biologically active peptide from the RAS, interacting with Mas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. In the present study, we investigated the effects of alamandine on ascending aorta remodelling after transverse aortic constriction (TAC) in mice. Methods and results: C57BL/6J male mice were divided into the following groups: Sham (sham-operated), TAC (operated) and TAC+ALA (operated and treated with alamandine-HPßCD (2-Hydroxypropyl-ß-cyclodextrin), 30 µg/kg/day, by gavage). Oral administration of alamandine for 14 days attenuated arterial remodelling by decreasing ascending aorta media layer thickness and the cells density in the adventitia induced by TAC. Alamandine administration attenuated ascending aorta fibrosis induced by TAC, through a reduction in the following parameters; total collagen deposition, expression collagen III and transforming growth factor-ß (TGF-ß) transcripts, matrix metalloproteinases (MMPs) activity and vascular expression of MMP-2. Importantly, alamandine decreased vascular expression of proinflammatory genes as CCL2, tumour necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß), and was able to increase expression of MRC1 and FIZZ1, pro-resolution markers, after TAC surgery. Conclusion: Alamandine treatment attenuates vascular remodelling after TAC, at least in part, through anti-fibrotic and anti-inflammatory effects. Hence, this work opens new avenues for the use of this heptapeptide also as a therapeutic target for vascular disease.
Asunto(s)
Antiinflamatorios/farmacología , Aorta Torácica/efectos de los fármacos , Enfermedades de la Aorta/prevención & control , Oligopéptidos/farmacología , Remodelación Vascular/efectos de los fármacos , Animales , Aorta Torácica/metabolismo , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/fisiopatología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Mediadores de Inflamación/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
We explored the impact of gender and cardiovascular risk factors (RF) in the distribution and burden of coronary and extra-coronary atherosclerotic plaques among patients undergoing ECG-gated thoracoabdominal computed tomography angiography (CTA) from the supra-aortic trunks to the femoral arteries. We included a consecutive cohort of patients who underwent ECG-gated thoracoabdominal aortic CTA from the supra-aortic trunks to the pubic symphysis. We evaluated the number of coronary segments with plaques [segment-involvement score (SIS)]; and the extra-coronary atherosclerotic plaque burden, comprising the aorta and supra-aortic trunks, iliofemoral arteries, and visceral arteries (extra-coronary SS). A total of 3400 vascular segments were evaluated in 100 patients (mean age 67.0 ± 12.6 years, 66% male). Seventy-two (72%) patients had evidence of atherosclerosis in the coronary tree (coronary SIS ≥ 1), of which 32% was extensive (coronary SIS > 5). Males had a significantly higher prevalence of coronary SIS ≥ 1 [53 (80%), vs. 19 (56%), p = 0.018], and coronary SIS > 5 [24 (36%) vs. 8 (24%), p = 0.035] than females. Extra-coronary SS was similar between genders (males 10.2 ± 5.8 vs. females 9.7 ± 5.4, p = 0.70), irrespective of the location along the different vascular beds. The number of coronary RF was significantly related to the coronary SIS (p = 0.038), and hypertension and diabetes were consistently related to coronary and extra-coronary plaque burden. In the present study involving analysis of multiple vascular beds from the supra-aortic trunks to the femoral arteries, we identified significant sex-related differences in coronary plaque burden, whereas extra-coronary plaque burden was similar between genders irrespective of the vascular bed assessed.
Asunto(s)
Enfermedades de la Aorta/diagnóstico por imagen , Aortografía/métodos , Arterias/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad Arterial Periférica/diagnóstico por imagen , Placa Aterosclerótica , Anciano , Anciano de 80 o más Años , Puntos Anatómicos de Referencia , Enfermedades de la Aorta/epidemiología , Enfermedades de la Aorta/patología , Arterias/patología , Técnicas de Imagen Sincronizada Cardíacas , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/patología , Electrocardiografía , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/patología , Humanos , Masculino , Persona de Mediana Edad , Cuello , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/patología , Valor Predictivo de las Pruebas , Prevalencia , Sínfisis Pubiana , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores SexualesAsunto(s)
Procedimientos Endovasculares/métodos , Fístula Esofágica/cirugía , Neoplasias Esofágicas/complicaciones , Fístula Vascular/cirugía , Angiografía/métodos , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Oclusión con Balón/instrumentación , Fístula Esofágica/etiología , Fístula Esofágica/patología , Esófago/patología , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Fístula Vascular/etiología , Fístula Vascular/patologíaRESUMEN
In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.
Asunto(s)
Aorta/efectos de los fármacos , Enfermedades de la Aorta/prevención & control , Aterosclerosis/tratamiento farmacológico , Fármacos Cardiovasculares/administración & dosificación , Colesterol en la Dieta , Lípidos/química , Metotrexato/administración & dosificación , Nanopartículas , Paclitaxel/administración & dosificación , Placa Aterosclerótica , Animales , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/patología , Fármacos Cardiovasculares/química , Citocinas/metabolismo , Modelos Animales de Enfermedad , Composición de Medicamentos , Quimioterapia Combinada , Mediadores de Inflamación/metabolismo , Liposomas , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Metotrexato/química , Paclitaxel/química , ConejosRESUMEN
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice. METHODS: We incubated VSMC from ob/ob mice and wild type C57BL/6 littermates with or without Bmp-2. We used loss-of-function experiments to investigate the role of Msx2 in Bmp-2-induced ob/ob VSMC osteochondrogenic differentiation and calcification by transfecting Msx2 siRNA into VSMC. RESULTS: Baseline ob/ob VSMC and aorta showed increased Msx2, Runx2, alkaline phosphatase mRNA and protein expression, which further increased in Bmp-2-incubated ob/ob VSMC, therefore augmenting ob/ob VSMC calcification in comparison to wild type VSMC. Accordingly, signaling pathways to induce VSMC osteogenic differentiation, such as Smad1/5 phosphorylation increased in ob/ob versus wild type aorta. In comparison to wild type VSMC, Msx2 siRNA transfected VSMC decreased Bmp-2-dependent osteochondrogenic differentiation response by abrogating Msx2, Runx2, Alpl expression in ob/ob but not in wild type VSMC. Nonetheless, Msx2 inhibition did not decrease calcification in Bmp-2 stimulated ob/ob VSMC in vitro. CONCLUSIONS: Our data support a crucial role of Msx2 for ob/ob VSMC osteochondrogenic differentiation, however, Msx2 signaling alone is not sufficient for ob/ob VSMC calcification after Bmp-2 stimulation in vitro. These findings can be translated into novel perspectives for the understanding of the mechanisms and to provide therapeutic targets underlying vascular calcification in type 2 diabetes.
Asunto(s)
Enfermedades de la Aorta/metabolismo , Proteínas de Homeodominio/metabolismo , Resistencia a la Insulina , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Obesidad/metabolismo , Osteoblastos/metabolismo , Osteogénesis , Calcificación Vascular/metabolismo , Animales , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Proteína Morfogenética Ósea 2/deficiencia , Proteína Morfogenética Ósea 2/genética , Células Cultivadas , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Resistencia a la Insulina/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Obesidad/genética , Obesidad/patología , Osteoblastos/patología , Fenotipo , Interferencia de ARN , Transducción de Señal , Transfección , Calcificación Vascular/genética , Calcificación Vascular/patologíaRESUMEN
INTRODUCTION:: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. OBJECTIVE:: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. METHOD:: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. RESULTS:: Microscopic atherosclerosis was higher in young subjects (early injury) and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. CONCLUSION:: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.
Asunto(s)
Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Aterosclerosis/etiología , Aterosclerosis/patología , Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática Alcohólica/patología , Alcoholismo/complicaciones , Aorta/patología , Índice de Masa Corporal , Colágeno/análisis , Femenino , Fibrosis/patología , Humanos , Masculino , Índice de Severidad de la Enfermedad , Factores Sexuales , Estadísticas no ParamétricasRESUMEN
Summary Introduction: Alcoholism is a major public health problem, which has a high social cost and affects many aspects of human activity. Liver disease is one of the first consequences of alcohol abuse, and steatosis, liver cirrhosis and hepatitis may occur. Other organs are also affected with pathological changes, such as pancreatitis, cardiomyopathies, dyslipidemias and atherosclerosis. Objective: To identify the occurrence and degree of atherosclerosis in alcohol-dependent individuals with liver cirrhosis, observing macroscopic and microscopic changes in lipid and collagen deposits and in the liver. We also aimed to verify the association of lipid and collagen fiber deposits with gender, age and body mass index, and to relate alcoholism, liver cirrhosis and atherosclerosis. Method: We performed a study based on autopsy reports of patients with alcoholic liver cirrhosis, with analysis of aorta and liver fragments to verify the occurrence and degree of atherosclerosis, as well as collagen contents. Results: Microscopic atherosclerosis was higher in young subjects (early injury) and in patients with alcoholic liver cirrhosis. The macroscopic analysis of atherosclerosis in aortas showed that patients in more advanced age groups presented more severe classifications. Atherosclerosis, both micro and macroscopically, and the percentage of fibrosis in the liver and aorta were more expressive in females. Conclusion: Cirrhotic patients presented a higher percentage of fibrosis and lipidosis, and may represent a group susceptible to the accelerated progression of cardiovascular diseases. Investigative studies contribute to targeting health-promoting interventions, reducing the mortality and costs of treating cardiovascular disease.
Resumo Introdução: O alcoolismo é um grande problema de saúde pública, de elevado custo social e que afeta vários aspectos da atividade humana. Hepatopatia é uma das primeiras consequências do abuso de álcool, podendo ocorrer esteatose, cirrose hepática e hepatite. Outros órgãos, porém, também são afetados, ocorrendo alterações patológicas, como pancreatite, cardiomiopatias, dislipidemias e aterosclerose. Objetivo: Identificar a ocorrência e a intensidade de aterosclerose em alcoolistas com cirrose hepática, observando alterações macro e microscópicas do depósito lipídico e de fibras colágenas e fígado. Verificar a associação de depósito lipídico e de fibras colágenas com gênero, idade e índice de massa corporal (IMC). Relacionar alcoolismo, cirrose hepática e aterosclerose. Método: Foi realizado estudo com base em laudos de autópsias de pacientes com cirrose hepática alcoólica, sendo estudados aortas e fígados para verificar a ocorrência e a intensidade de aterosclerose, bem como a quantidade de colágeno encontrada. Resultados: A aterosclerose microscópica foi maior em jovens (lesão inicial) e em pacientes com cirrose hepática alcoólica. A análise macroscópica da aterosclerose nas aortas mostrou que pacientes com faixas etárias mais avançadas apresentaram classificações mais intensas. A aterosclerose, tanto micro quanto macroscopicamente, e a porcentagem de fibrose no fígado e na aorta foram mais expressivas no gênero feminino. Conclusão: Os pacientes cirróticos apresentaram maior porcentagem de fibrose e lipidose, e podem representar um grupo susceptível à acelerada progressão de doenças cardiovasculares. Estudos investigativos contribuem para o direcionamento das intervenções promotoras da saúde, reduzindo a mortalidade e os custos no tratamento das doenças cardiovasculares.
Asunto(s)
Humanos , Masculino , Femenino , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Aterosclerosis/etiología , Aterosclerosis/patología , Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática Alcohólica/patología , Aorta/patología , Índice de Severidad de la Enfermedad , Fibrosis/patología , Índice de Masa Corporal , Factores Sexuales , Colágeno/análisis , Estadísticas no Paramétricas , Alcoholismo/complicacionesRESUMEN
La tetralogía de Fallot es una enfermedad congénita rara, caracterizada por estenosis de la válvula pulmonar, hipertrofia ventricular derecha, comunicación interventricular y dextroposición de la arteria aorta. La fisiopatología y las características clínicas con que se presenta dependen principalmente del grado de obstrucción de la arteria pulmonar. Desde el punto de vista clínico, los animales presentan cianosis, resistencia al ejercicio, disnea y síncopes. El diagnóstico definitivo y el pronóstico se obtienen mediante ecocardiografía (Doppler). Si bien la cirugía es el único método efectivo de tratamiento, en casos menos graves, existen medicamentos que actúan de manera paliativa. Este trabajo relata el caso de un perro mestizo de once meses con diagnóstico de tetralogía de Fallot, haciendo énfasis en la ecocardiografia (Doppler) como método de diagnóstico definitivo.
Tetralogy of Fallot is a rare congenital disease consisting of pulmonary valve stenosis, right ventricular hypertrophy, ventricular septal defect and aortic dextroposition. Pathophysiological consequences and clinical presentation depend mainly on the degree of pulmonary artery obstruction. Symptoms include cyanosis, exercise intolerance, dyspnea, and syncope. Definitive diagnosis and prognosis are obtained by Doppler echocardiography. Surgery is the only effective method of treatment, however, pharmacotherapy may be indicated as palliative treatment in mild cases of the disease. This work reports on the case of an eleven-month-old mongrel, diagnosed with tetralogy of Fallot and highlights the importance of Doppler echocardiography as the definitive diagnostic tool for this disease.
A tetralogia de Fallot é urna rara doença congênita, definida por estenose da valva pulmonar, hipertrofia ventricular direita, defeito do septo interventricular e dextroposição da aorta. Suas consequências fisiopatológicas, assim como a apresentação clínica, dependem principalmente do grau de obstrução da artéria pulmonar. Clinicamente, os animais apresentam cianose, intolerância ao exercício, dispneia e síncopes. O diagnóstico definitivo e o prognóstico são obtidos por meio da ecodopplercardiografia. A cirurgia é o único método efetivo para o tratamento; no entanto, em casos brandos, a terapia medicamentosa pode ser indicada como forma paliativa. O presente trabalho relata o caso de um cão de onze meses de idade, sem raça definida, diagnosticado com tetralogia de Fallot, enfatizando a ecoclopplercardiografia como método diagnóstico definitivo da doença.
Asunto(s)
Animales , Perros , Diagnóstico/diagnóstico , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/fisiopatología , Cardiopatías Congénitas/terapia , Cardiopatías Congénitas/veterinaria , Tetralogía de Fallot/patología , Tetralogía de Fallot/terapia , Tetralogía de Fallot/veterinaria , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/veterinaria , Arteria Pulmonar/fisiopatología , Cianosis/diagnóstico , Cianosis/patología , Cianosis/veterinaria , Defectos del Tabique Interventricular/diagnóstico , Defectos del Tabique Interventricular/veterinaria , Enfermedades de la Aorta/congénito , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/veterinaria , Procedimientos Quirúrgicos Operativos/veterinariaRESUMEN
La tetralogía de Fallot es una enfermedad congénita rara, caracterizada por estenosis de la válvula pulmonar, hipertrofia ventricular derecha, comunicación interventricular y dextroposición de la arteria aorta. La fisiopatología y las características clínicas con que se presenta dependen principalmente del grado de obstrucción de la arteria pulmonar. Desde el punto de vista clínico, los animales presentan cianosis, resistencia al ejercicio, disnea y síncopes. El diagnóstico definitivo y el pronóstico se obtienen mediante ecocardiografía (Doppler). Si bien la cirugía es el único método efectivo de tratamiento, en casos menos graves, existen medicamentos que actúan de manera paliativa. Este trabajo relata el caso de un perro mestizo de once meses con diagnóstico de tetralogía de Fallot, haciendo énfasis en la ecocardiografia (Doppler) como método de diagnóstico definitivo.(AU)
Tetralogy of Fallot is a rare congenital disease consisting of pulmonary valve stenosis, right ventricular hypertrophy, ventricular septal defect and aortic dextroposition. Pathophysiological consequences and clinical presentation depend mainly on the degree of pulmonary artery obstruction. Symptoms include cyanosis, exercise intolerance, dyspnea, and syncope. Definitive diagnosis and prognosis are obtained by Doppler echocardiography. Surgery is the only effective method of treatment, however, pharmacotherapy may be indicated as palliative treatment in mild cases of the disease. This work reports on the case of an eleven-month-old mongrel, diagnosed with tetralogy of Fallot and highlights the importance of Doppler echocardiography as the definitive diagnostic tool for this disease.(AU)
A tetralogia de Fallot é urna rara doença congênita, definida por estenose da valva pulmonar, hipertrofia ventricular direita, defeito do septo interventricular e dextroposição da aorta. Suas consequências fisiopatológicas, assim como a apresentação clínica, dependem principalmente do grau de obstrução da artéria pulmonar. Clinicamente, os animais apresentam cianose, intolerância ao exercício, dispneia e síncopes. O diagnóstico definitivo e o prognóstico são obtidos por meio da ecodopplercardiografia. A cirurgia é o único método efetivo para o tratamento; no entanto, em casos brandos, a terapia medicamentosa pode ser indicada como forma paliativa. O presente trabalho relata o caso de um cão de onze meses de idade, sem raça definida, diagnosticado com tetralogia de Fallot, enfatizando a ecoclopplercardiografia como método diagnóstico definitivo da doença.(AU)
Asunto(s)
Animales , Perros , /diagnóstico , Tetralogía de Fallot/veterinaria , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/veterinaria , Tetralogía de Fallot/patología , Tetralogía de Fallot/terapia , Cardiopatías Congénitas/fisiopatología , Cardiopatías Congénitas/terapia , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/veterinaria , Cianosis/diagnóstico , Cianosis/patología , Cianosis/veterinaria , Procedimientos Quirúrgicos Operativos/veterinaria , Arteria Pulmonar/fisiopatología , Enfermedades de la Aorta/congénito , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/veterinaria , Defectos del Tabique Interventricular/diagnóstico , Defectos del Tabique Interventricular/veterinariaRESUMEN
RESUMEN Introducción: Es un un proceso de la pared aórtica en el cual se encuentran la disección aórtica, el hematoma intramural y la úlcera penetrante. Cabe destacar que la transección de aorta traumática se considera como parte del síndrome, no reflejado aquí, al no tratar traumatismos.Objetivos: Realizar un relevamiento acerca de las características demográficas, diagnóstico y tratamiento en nuestro equipo de trabajo.Materiales y métodos: Se evaluaron edad, sexo, comorbilidades, cuadro clínico y laboratorio al ingreso, métodos de diagnósticos por imágenes, tratamiento y tiempo de internación. Resultados: Siete pacientes presentaron disección de aorta tipo B, dos pacientes hematomas intramurales; uno junto a una ulcera aórtica y otro a disección crónica tipo B y uno presentó úlcera de aorta torácica doble sintomática asociada a aneurisma de aorta abdominal. El 80% de los pacientes fueron de sexo masculino, con un promedio de edades de 64,7. El promedio de días de internación fue de 19,8. El dolor se presentó en nueve de los pacientes. En todos se realizó angiotomografía axial computada. La totalidad fueron tratados por medio de endoprótesis de aorta. Conclusión: 1- El síndrome aórtico agudo es una patología de elevada mortalidad cuyo diagnóstico puede ser alcanzado en forma rápida por una evaluación básica y un apoyo imagenológico. 2- Consideramos que la tomografía es el método que más precisiones aporta acerca de las características morfológicas, diagnósticas y para las mediciones para el tratamiento endovascular. 3- El tratamiento endovascular es la opción más efectiva que reduce la mortalidad, la estancia nosocomial y las complicaciones. (AU)
Asunto(s)
Masculino , Femenino , Aorta Torácica/diagnóstico por imagen , Enfermedades de la Aorta/patología , TomografíaRESUMEN
The objective of this study is to characterize arterial tissue with and without atherosclerosis by fluorescence lifetime imaging microscopy (FLIM) using Europium Chlortetracycline complex (EuCTc) as fluorescent marker. For this study, twelve rabbits were randomly divided into a control group (CG) and an experimental group (EG), where they were fed a normal and hypercholesterolemic diet, respectively, and were treated for 60 days. Cryosections of the aortic arch specimens were cut in a vertical plane, mounted on glass slides, and stained with Europium (Eu), Chlortetracycline (CTc), Europium Chlortetracycline (EuCTc), and Europium Chlortetracycline Magnesium (EuCTcMg) solutions. FLIM images were obtained with excitation at 405 nm. The average autofluorescence lifetime within plaque depositions was ~1.36 ns. Reduced plaque autofluorescence lifetimes of 0.23 and 0.31 ns were observed on incubation with EuCTc and EuCTcMg respectively. It was observed a quenching of collagen, cholesterol and TG emission spectra increasing EuCTc concentration. The drastic reduction in fluorescence lifetimes is due to a resonant energy transfer between collagen, triglycerides, cholesterol and europium complexes, quenching fluorescence.
Asunto(s)
Aorta Torácica/patología , Enfermedades de la Aorta/patología , Aterosclerosis/patología , Clortetraciclina/química , Europio/química , Colorantes Fluorescentes/química , Microscopía Fluorescente , Placa Aterosclerótica , Animales , Aorta Torácica/metabolismo , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/metabolismo , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Clortetraciclina/análogos & derivados , Colesterol en la Dieta/metabolismo , Colágeno/metabolismo , Modelos Animales de Enfermedad , Transferencia de Energía , Conejos , Factores de Tiempo , Triglicéridos/metabolismoRESUMEN
Lymphocytes, the cellular effectors of adaptive immunity, are involved in the chronic inflammatory process known as atherosclerosis. Proatherogenic and atheroprotective properties have been ascribed to B cells. However, information regarding the role of B cells during atherosclerosis is scarce. Both the frequency and the phenotype of B cell subpopulations were studied by flow cytometry in wild type and apolipoprotein-E-deficient (apoE(-/-)) mice fed a high-fat (HFD) or control diet. Whereas the proportion of follicular cells was decreased, transitional 1-like cells were increased in mice with advanced atherosclerotic lesions (apoE(-/-) HFD). B cells in atherosclerotic mice were more activated, indicated by their higher surface expression of CD80, CD86, CD40 and CD95 and increased serum IgG1 levels. In the aorta, a decreased frequency of B cells was observed in mice with advanced atherosclerosis. Low expression of CD19 was observed on B cells from the spleen, aorta and lymph nodes of apoE(-/-) HFD mice. This alteration correlated with serum levels of IgG1 and cholesterol. A reduction in CD19 expression was induced in splenic cells from young apoE(-/-) mice cultured with lipemic serum. These results show that mice with advanced atherosclerosis display a variety of alterations in the frequency and phenotype of B lymphocytes, most of which are associated with dyslipidemia.
Asunto(s)
Aorta/inmunología , Enfermedades de la Aorta/inmunología , Aterosclerosis/inmunología , Subgrupos de Linfocitos B/inmunología , Dislipidemias/inmunología , Animales , Antígenos CD/sangre , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/sangre , Aterosclerosis/genética , Aterosclerosis/patología , Subgrupos de Linfocitos B/metabolismo , Biomarcadores/sangre , Células Cultivadas , Quimiotaxis de Leucocito , Colesterol/sangre , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Dislipidemias/sangre , Dislipidemias/genética , Femenino , Citometría de Flujo , Predisposición Genética a la Enfermedad , Inmunoglobulina G/sangre , Inmunofenotipificación/métodos , Recuento de Linfocitos , Ratones Noqueados , FenotipoAsunto(s)
Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Stents , Aorta Torácica/patología , Coartación Aórtica/patología , Coartación Aórtica/cirugía , Enfermedades de la Aorta/patología , Aortografía , Niño , Femenino , Humanos , Encefalopatía Hipertensiva/patología , Diseño de Prótesis , Síndrome , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Niño , Femenino , Humanos , Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Stents , Aortografía , Aorta Torácica/patología , Coartación Aórtica/patología , Coartación Aórtica/cirugía , Enfermedades de la Aorta/patología , Encefalopatía Hipertensiva/patología , Diseño de Prótesis , Síndrome , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Objetivo: Determinar a prevalência e as características de ateromatose da aorta ascendente e/ou arco aórtico em cirurgia cardiovascular, os fatores de risco de sua ocorrência e a implicação prognóstica imediata da mesma. Métodos: No período de janeiro de 2007 a junho de 2011, 2042 pacientes adultos consecutivos foram analisados, sem critérios de exclusão. A detecção de ateromatose da aorta foi realizada por meio de palpação durante o ato operatório. Os fatores de risco de ateromatose da aorta e a sua implicação prognóstica foram determinados por regressão logística multivariada. Resultados: A prevalência de ateromatose da aorta foi de 3,3% (68 pacientes). Os fatores de risco foram a idade > 61 anos (OR= 2,79; IC95%= 2,43 - 3,15; P<0,0001), doença arterial coronária (OR=3,1; IC95%=2,8 - 3,44; P=0,002), hipertensão arterial sistêmica (OR=2,26; IC95%=1,82 - 2,7; P=0,03) e doença vascular periférica (OR=3,15; IC95%= 2,83 - 3,46; P=0,04). A ateromatose da aorta foi preditor independente da ocorrência de acidente vascular cerebral no pós-operatório (OR=3,46; IC95%=3,18 - 3,76; P=0,01). Conclusão: Embora infrequente, a presença de ateromatose da aorta tem maior ocorrência de acordo com a idade, com a presença de hipertensão arterial sistêmica, doença arterial coronária e doença vascular periférica. Nestas situações, é justificada investigação pré e intraoperatória mais detalhada, pois a presença de ateromatose determina maior chance de acidente vascular cerebral no pós-operatório. .
Objective: To determine the prevalence and profile of ascending aorta or aortic arch atheromatous disease in cardiovascular surgery patients, its risk factors and its prognostic implication early after surgery. Methods: Between January 2007 and June 2011, 2042 consecutive adult patients were analyzed, with no exclusion criteria. Atheromatous aorta diagnosis was determined intraoperatively by surgeon palpation of the aorta. Determinants of atheromatous aorta, as well as its prognostic implication were studied by multivariate logistic regression. Results: Prevalence of atheromatous aorta was 3.3% (68 patients). Determinants were age > 61 years (OR= 2.79; CI95%= 2.43 - 3.15; P<0.0001), coronary artery disease (OR=3.1; CI95%=2.8 - 3.44; P=0.002), hypertension (OR=2.26; CI95%=1.82 - 2.7; P=0.03) and peripheral vascular disease (OR=3.15; CI95%= 2.83 - 3.46; P=0.04). Atheromatous aorta was an independent predictor of postoperative cerebrovascular accident (OR=3.46; CI95%=3.18 - 3.76; P=0.01). Conclusion: Although infrequent, the presence of atheromatous aorta is associated with advanced age, hypertension, coronary artery disease and peripheral vascular disease. In those patients, a more detailed preoperative and intraoperative assessment of the aorta is justified, due to greater risk of postoperative cerebrovascular accident. .
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Enfermedades de la Aorta/epidemiología , Procedimientos Quirúrgicos Cardiovasculares , Placa Aterosclerótica/epidemiología , Factores de Edad , Enfermedades de la Aorta/patología , Brasil/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Métodos Epidemiológicos , Hipertensión/complicaciones , Complicaciones Posoperatorias , Pronóstico , Enfermedades Vasculares Periféricas/complicaciones , Placa Aterosclerótica/patología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
We describe herein a case of a patient who, when in orthostatic positions, had severe hypoxemia and ventilatory dysfunction. Although the severity of symptoms required hospitalization in an intensive care setting, the initial tests only identified the presence of enlarged aortic root, which did not explain the condition. The association of these events with an unusual etiology, namely intracardiac shunt, characterized the diagnosis of platypnea-orthodeoxia syndrome. The literature review shows that, with advancing research methods, there was a progressive increase in the identification of this condition, and this association should be part of the differential diagnosis of dyspnea in patients with enlarged aortic root.