Les hormones thyroïdiennes jouent un rôle dans de nombreux processus métabolique tels que le développement, la croissance et le contrôle du métabolisme. Les HT se fixent sur leurs récepteurs nucléaires, les TR (TRalpha et beta). Ces TR sont des facteurs de transcription dont l’activité est contrôlée par la fixation de leur ligand, ils appartiennent à la super famille des récepteurs nucléaires d’hormone. Au cours de ma thèse je me suis intéressée aux rôles des TR dans deux contextes particuliers. Dans un premier temps, j’ai pu mettre en évidence le rôle de TRbeta dans la régulation du métabolisme hépatique via l’activation d’un gène clé ChREBP permettant la détection du glucose. Par l’utilisation d’animaux transgéniques et des systèmes in vitro, j’ai pu montrer que TRbeta régule positivement l’expression de ChREBP via le fixation sur son élément de réponse présent de le promoteur. Nous avons pu montrer que cette activation est isoforme spécifique, indépendante d’un autre récepteur nucléaire LXR. Dans un deuxième temps, j’ai montré que l’autre isoforme de TR, TRalpha est impliqué dans le développement de l’athérosclérose, une maladie cardiovasculaire. Par l’utilisation d’un modèle de souris transgénique, j’ai pu mettre en évidence que TRalpha possède à la fois un rôle anti-inflammatoire et également il est capable de stimuler l’élimination du cholestérol par les macrophages. L’absence de ce récepteur induit une augmentation du développement de la maladie ainsi que des cytokines circulantes chez la souris. Par l’utilisation d’un système in vitro, j’ai pu mettre en évidence que l’absence de TRalpha diminue l’efflux de cholestérol dans les macrophages de souris. Ces données suggèrent un nouveau rôle des HT/TR dans le développement de pathologies humaines, notamment un effet anti-inflammatoire longtemps supposer mais mis en évidence que très récemment. / Thyroid hormones (TH) play a role in many processes such as development, growth and metabolic control. HT bind to their nuclear receptors, the TR (TRalpha and beta). TRs belong to the superfamily of nuclear hormone receptors. These TRs are transcription factors whose activity is controlled by the binding of their ligand. During my PhD thesis I focused on the roles of TR in two contexts. Initially, I highlighted the role of TRbeta in the regulation of the hepatic metabolism via the activation of the key gene ChREBP, a glucose-responsive transcription factor. Using transgenic animal models and in vitro systems, I showed that TRbeta up regulates the expression of ChREBP via binding to its response element present in the promoter. I have shown that this activation is isoform specific and independent of another nuclear receptor LXR. In a second part, I demonstrated that the TRalpha isoform is involved in the development of atherosclerosis, a cardiovascular disease. Using a transgenic mice model, I observed that TRalpha has an anti-inflammatory effect and it is also able to stimulate the reverse cholesterol transport by macrophages. The absence of this receptor induces an increase in the development of the disease as well as in the level of circulating cytokines in mice. The deletion of TRalpha decreases the cholesterol efflux in bone marrow derived macrophages in vitro and it is correlated with a decrease of ABCA1 expression. All these data suggest a novel role of HT / TR in the development of human pathologies, including an anti-inflammatory role assumed, but recently demonstrated.

La compréhension des mécanismes précis conduisant à la formation d'une plaque d'athérosclérose et à sa déstabilisation provoquant infarctus du myocarde ou accident vasculaire cérébral est fondamentale pour l'amélioration de la prévention, du dépistage et du traitement. Notre travail de thèse a porté sur l'analyse et le développement des modalités d'imagerie de la plaque d'athérosclérose afin d'améliorer notre capacité à suivre in vivo l'évolution de cette maladie. Nous proposons, après une introduction sur l'athérosclérose et la notion de plaque vulnérable, une revue des modèles animaux d'athérosclérose et l'intérêt du suivi en imagerie par résonance magnétique. Différentes modalités permettent le suivi en imagerie de la plaque d'athérosclérose. En pratique clinique, l'Imagerie par Résonance Magnétique (IRM) haute résolution est reconnue comme étant une modalité fiable et reproductible de caractérisation morphologique de la plaque carotidienne. Nous démontrons que l'injection de Gadolinium utilisée classiquement pour visualiser la lumière des vaisseaux permet également de préciser la caractérisation de la plaque carotidienne en donnant des informations sur la néovascularisation, la matrice extracellulaire et son statut inflammatoire. La caractérisation fonctionnelle de la plaque peut également être appréciée par l'injection de particules de fer en IRM ou par l'injection de radio-traceur comme le 18Ffluorodesoxyglucose en Tomographie par Emission de Positron (TEP). Le couplage de l'IRM et de la TEP de développement récent nous a permis de montrer une plus grande sensibilité de signal en TEP qu'en IRM avec particules de fer pour détecter les changements inflammatoires observés dans des plaques d'athérome d'aorte de lapin. Les applications actuelles de l'imagerie de l'athérosclérose sont nombreuses permettant de juger de l'efficacité thérapeutique d'un médicament ou d'identifier les patients à plus haut risque d'évènement cardiovasculaire / A better understanding of mechanisms leading to the formation of an atherosclerotic plaque and its destabilization causing myocardial infarction or stroke is fundamental to improve prevention, detection and treatment. Our work focused on development of imaging modalities of atherosclerotic plaque in order to improve our ability to monitor in vivo the progression of this disease. We propose, after an introduction to the concept of atherosclerosis and vulnerable plaque, a review of existing animal models of atherosclerosis and the interest of monitoring with magnetic resonance imaging. Different methods allow imaging of atherosclerotic plaque. In clinical practice, Magnetic Resonance Imaging (MRI) is recognized as a reliable and reproducible tool for morphological characterization of carotid plaque. We demonstrate that Gadolinium conventionally used to visualize the lumen of the vessels also allows a characterization of carotid plaque with information on neovascularization, extracellular matrix and inflammatory status. The functional characterization of the atherosclerotic plaque can be assessed with iron particles in MRI or with radiotracer such as 18Ffluorodeoxyglucose in positron emission tomography (PET). Combined PET-MR systems allowed us to show a better sensitivity of PET signal than USPIO-MR signal to detect early inflammatory changes in atherosclerotic plaque of rabbit aorta. We also provide some current clinical applications of atherosclerosis imaging (drug efficacy or identification of high risk patients)

No description available.

O objetivo deste estudo clínico randomizado duplo-cego foi avaliar o efeito da suplementação oral de zinco e selênio concomitante ao tratamento com rosuvastatina sobre os marcadores de estresse oxidativo e inflamação, bem como o status de zinco e selênio, em pacientes com aterosclerose, apresentando angina estável. A amostragem foi composta por adultos e idosos, 47 homens e 29 mulheres, com diagnóstico de aterosclerose coronariana por angiografia, atendidos no Serviço de Hemodinâmica do Natal Hospital Center - Natal / RN. O projeto foi aprovado pelos Comitês de Ética em Pesquisa da UFRN e da FCF-USP. A coleta de dados foi realizada no primeiro momento e após 4 meses do tratamento com rosuvastatina 10 mg, concomitante à suplementação com zinco (30mg/d) e selênio (150µg/d), ou placebo, sendo avaliados os parâmetros antropométricos e dietéticos, zinco e selênio plasmáticos e eritrocitários, perfil lipídico, LDL minimamente oxidada, anticorpos anti-LDL(-), imunocomplexos Ac-LDL(-), GPx, SOD, IL-6 e PCR-as. Houve predominância do gênero masculino, idade média em torno de 60 anos, ex-fumantes, portadores de hipertensão arterial, alta freqüência do sobrepeso/obesidade e circunferência abdominal aumentada/muito aumentada. As dietas caracterizaram-se como hipocalórica, hiperprotéica, normoglicídica e hipolípídica, com baixo teor de fibra e altas prevalências de inadequação de ingestão de zinco e selênio. O status de zinco e selênio no plasma e eritrócitos não foi alterado significativamente nos grupos placebo e suplementado entre os dois momentos do estudo. A terapia com a rosuvastatina mostrou-se eficaz na redução das concentrações de colesterol total, LDL, colesterol não-HDL, triacilgliceróis e PCR-as, independente da suplementação com os minerais zinco e selênio. As concentrações de LDL(-), Ac anti-LDL(-), imunocomplexos, IL-6 e as atividades das enzimas SOD e GPx não foram modificadas em função das intervenções com rosuvastatina associadas ou não à suplementação. Conclui-se que o tratamento com rosuvastatina 10mg durante 4 meses não alterou o status de zinco e selênio considerando os biomarcadores avaliados. A suplementação de zinco e selênio não influenciou os biomarcadores de estresse oxidativo e inflamação. Estudos adicionais serão necessários para avaliação da necessidade de suplementação neste grupo de pacientes com aterosclerose, analisando-se outras doses, tempo de suplementação e biodisponibilidade da forma química dos minerais prescritos. / The aim of this randomized double-blind study was to evaluate the effect of oral zinc and selenium supplementation, concomitant with rosuvastatin treatment, on markers of oxidative stress and inflammation, as well as the status of zinc and selenium in adult patients with atherosclerosis and stable angina. The study included 47 men and 29 women, average age around 60 years, with coronary atherosclerosis diagnosed by angiography at the Hemodynamic Service at Natal Hospital Center - Natal / RN. The project was approved by the Ethics Committee of UFRN and FCF-USP. Data from patients were obtained at beggining and after four months of treatment with 10 mg rosuvastatin, concomitantly with zinc (30mg/d) and selenium (150µg/d) supplementation or placebo. The anthropometric and dietary data, zinc and selenium concentrations in plasma and erythrocyte, lipid profile, electronegative LDL (LDL(-)), anti- electronegative LDL, Ac-LDL(-) immune complexes, GPx and SOD activities, IL-6 and hs-CRP were evaluated in all patients. Most patients were former smokers with arterial hypertension, high rate of overweight/obesity and increased waist circumference. The diets contained low-calorie, hyperproteic, normoglycidic, low-fat and fiber content and inadequate intake of zinc and selenium. The status of zinc and selenium in plasma and erythrocytes was not changed significantly in the supplemented and placebo groups between the two moments of the study. Rosuvastatin therapy was effective in reducing total cholesterol, LDL, non-HDL cholesterol, triglycerides and hs-CRP level, regardless of supplementation with the minerals zinc and selenium. The concentrations of LDL (-), anti- LDL (-), immune complexes, IL-6 and the activities of SOD and GPx were not modified by zinc and selenium supplementation associated with rosuvastatin. In conclusion, the treatment with 10 mg rosuvastatin for 4 months did not change either the status of zinc and selenium or the biomarkers evaluated in this study. Zinc and selenium supplementation did not affect oxidative stress and inflammation biomarkers. Additional studies are needed to evaluate the need for antioxidant minerals supplementation in patients with atherosclerosis, mainly to investigate other doses, duration of supplementation and bioavailability of the chemical form of the prescribed minerals.

Le déclin des hormones sexuelles avec l'âge a été mis en cause dans le développement de nombreuses maladies. Chez les hommes, la baisse de la testostérone circulante est un prédicteur de la mortalité toutes causes mais son impact sur le risque cardiovasculaire est incertain. A partir de l’étude de cohorte des Trois Cités (3C), réalisée en France dans la population générale, j'ai étudié le rôle de la testostérone plasmatique dans la survenue des évènements artériels ischémiques chez les hommes de plus de 65 ans.J'ai montré, dans une première partie, que des taux diminués de testostérone étaient associés à des facteurs de risque cardiovasculaire. J'ai notamment confirmé le rôle central de la masse grasse et du diabète comme déterminants des androgènes. De plus, j'ai mis en évidence une association inverse entre la testostérone et l’épaisseur intima-media (EIM) des artères carotidiennes. J'ai montré que cette relation dépendait du statut inflammatoire systémique avec des variations significatives de l'EIM observées uniquement chez les hommes ayant des niveaux élevés de protéine C-réactive. En revanche, aucune association significative n'a pu être détectée entre les androgènes et la présence de plaques d'athérome.Dans une seconde partie, j'ai mis en évidence une relation originale en forme de J entre la testostérone et le risque de maladies artérielles ischémiques. Les hommes ayant des taux élevés ou diminués de testostérone présentaient un risque accru d’évènements artériels et cette relation ne dépendait pas des principaux facteurs de risque cardiovasculaire. Des résultats similaires étaient observés pour les cardiopathies ischémiques et les accidents vasculaires cérébraux ischémiques.Ces résultats suggèrent que des taux moyens de testostérone totale circulante (4-5 ng/mL) protègent des maladies artérielles ischémiques. Ce rôle modulateur des androgènes pourrait être lié à un processus de vieillissement précoce non spécifique. / The age-related decline in sex hormones has been involved in the development of many diseases. In men, low endogenous testosterone levels predict mortality due to all causes. However, the role of testosterone in the development of cardiovascular disease remains uncertain. In the french Three-City population-based cohort study, I assessed the association of plasma sex hormones with the incidence of ischemic arterial disease in men aged over 65 years.First, I showed that low testosterone levels were associated with cardiovascular risk factors. I confirmed a leading role of obesity and diabetes as determinants of androgens. I also found an inverse association between testosterone and carotid intima-media thickness (IMT). I highlighted that, this relationship was mediated through systemic inflammation as significant changes in IMT were observed only in men with high C-reactive protein levels. However, no significant association was detected between androgens and the presence of carotid plaques.Second, I found an original J-shaped association between testosterone and risk of ischemic arterial disease. Men with elevated or decreased testosterone levels had higher risk of arterial events and this association was independent of major cardiovascular risk factors. Similar results were observed for ischemic heart disease and ischemic stroke.Overall, these results suggest that intermediate testosterone levels (4-5 ng/mL) could protect against cardiovascular events. Androgens could also be involved in general ageing process.

Moderate consumption of red wine has been widely associated with reduced cardiovascular risk, mainly due to its composition in phenolic compounds with antioxidant activity, such as trans-resveratrol. Our aim was to compare the effect of red wine vs trans-resveratrol consumption on the prevention and regression of atherosclerosis in LDLr (-/-) mice. This study consisted of two protocols: \"PREVENTION\" (PREV) and \"REGRESSION\" (REGR). Both protocols included four groups: red wine (WINE), dealcoholized red wine (EXT), trans-resveratrol (RESV), and control (CONT). In PREV protocol, animals received a normal diet for 8 weeks and then switched to an atherogenic diet for the following 8 weeks, while the opposite was performed during REGR protocol. Animals that received atherogenic diet after an initial period on a normal diet (PREV) gained more body weight (39.25 ± 2.30%) than the opposite (29.27 ± 1.91%, p=0.0013), suggesting an interaction between age and weight gain. Trans-resveratrol showed the highest hypocholesterolemic effect in PREV protocol, reducing total cholesterol, LDL-C and VLDL-C, but also HDL-C. The supplementation with trans-resveratrol and dealcoholized red wine changed the fatty acids profile in the liver in both protocols, leading to an increase of MDA concentrations and SOD activity in PREV protocol. All three forms of supplementation altered biomarkers of oxidative stress and lipidemia but presented no effect on the prevention or regression of fatty streaks. These results suggest that the cardiovascular protection associated with the \"French Paradox\" may be a result of synergistic effects between wine and the Mediterranean diet. / O consumo moderado de vinho tinto tem sido amplamente associado à redução do risco cardiovascular, principalmente devido à sua composição em compostos fenólicos com atividade antioxidante, como o trans-resveratrol. Nosso objetivo foi o de comparar o efeito do consumo de vinho tinto vs trans-resveratrol na prevenção e regressão da aterosclerose em camundongos LDLr (-/-). Este estudo consistiu em dois protocolos: \"PREVENÇÃO\" (PREV) e \"REGRESSÃO\" (REGR). Ambos os protocolos incluíram quatro grupos: vinho tinto (WINE), vinho tinto sem álcool (EXT), transresveratrol (RESV) e controle (CONT). No protocolo PREV, os animais receberam uma dieta normal durante 8 semanas e trocaram para uma dieta aterogênica durante as 8 semanas seguintes, enquanto o oposto foi realizado no protocolo REGR. Os animais que receberam dieta aterogênica após um período inicial em dieta normal (PREV) ganharam mais peso corporal (39.25 ± 2.30%) do que o oposto (29.27 ± 1.91%, p=0.0013), sugerindo uma interação entre idade e ganho de peso. O trans-resveratrol mostrou efeito hipocolesterolêmico mais elevado no protocolo PREV, reduzindo colesterol total, LDL-C e VLDL-C, mas também o HDL-C. A suplementação com trans-resveratrol e vinho tinto sem álcool alterou o perfil de ácidos graxos do fígado em ambos os protocolos, levando a um aumento das concentrações de MDA e da atividade da SOD no protocolo PREV. Todas as três formas de suplementação alteraram biomarcadores do estresse oxidativo e lipidemia, mas não apresentaram efeito sobre a prevenção ou regressão de estrias gordurosas. Esses resultados sugerem que a proteção cardiovascular associada ao \"Paradoxo francês\" pode ser resultado de efeitos sinérgicos entre o vinho e a dieta mediterrânea.

Introdução: Estudos clínicos e epidemiológicos têm revelado aumento do risco de doença coronária nos pacientes portadores de diabetes mellitus. A progressão da aterosclerose coronária documentada angiograficamente é identificada e utilizada com freqüência na prática clínica. Entretanto, o seu significado prognóstico ainda é pouco conhecido. Neste estudo, analisamos o significado dessa progressão em uma amostra de pacientes diabéticos e não diabéticos, portadores de doença arterial coronária e submetidos ao tratamento clínico, angioplastia ou cirurgia. Métodos. Foram avaliados 392 pacientes com cineangiocoronariografia inicial e após cinco anos de seguimento. A progressão foi definida como o surgimento de uma nova lesão ou o aumento em cerca de 20% de uma lesão prévia. A identificação da progressão foi realizada em pacientes submetidos previamente aos tratamentos clínico, cirúrgico e angioplastia. A progressão da doença foi analisada nos territórios correspondentes das artérias descendente anterior, circunflexa e coronária direita. A amostra englobou um grupo de 138 pacientes diabéticos e 254 pacientes não diabéticos. Dos 392 pacientes da amostra, formaram-se os seguintes grupos de intervenção: RCM (n=136) - 57 diabéticos e 79 não diabéticos; ATC (n=146) - 42 diabéticos e 104 não diabéticos; TM (n=110) - 38 diabéticos e 72 não diabéticos. Também se analisou também o percentual de progressão da doença, correlacionando-a com os fatores de risco e com a necessidade de novas intervenções. Resultados. Não se observou nenhuma diferença entre os grupos diabéticos e não diabéticos quanto à idade, sexo, HAS, tabagismo e distúrbios lipídicos. Além disso, não se demonstraram diferenças de progressão nesta amostra, quando comparados o grupo dos diabéticos e o de não diabéticos; entretanto, quando estratificados por intervenção, observou-se menor progressão da doença nos pacientes do grupo cirúrgico com diabetes mellitus (69,7%, p=0,014). Por outro lado, observou-se maior progressão no território das artérias descendente anterior (71,5%) e coronária direita (64,3%) dos pacientes diabéticos submetidos à angioplastia (p=0,024, p=0,047). Conclusão. Os resultados deste estudo permitiram concluir que, em cinco anos, o diabetes mellitus não impôs maior progressão angiográfica da doença aterosclerótica quando se compararam os grupos de pacientes diabéticos e de não diabéticos. Entretanto, a análise dos pacientes diabéticos submetidos a ATC revelou significativo aumento da progressão da doença nos territórios da coronária direita e da descendente anterior. Por outro lado, os pacientes diabéticos do grupo cirúrgico apresentaram menor progressão da doença. / Background: Epidemiologic and clinical studies have shown an increased risk of coronary artery disease (CAD) among patients with diabetes mellitus (DM). Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end-point in clinical trials; however, its prognostic significance is unclear. In this study, we prospectively analyzed the angiographic progression in diabetic and nondiabetic patients treated by medication, angioplasty or surgery. Methods: At baseline and 5- year follow-up angiograms were obtained in 392 randomized patients. Progression was defined as an increase in diameter of stenosis by >20% of at least one coronary lesion. We tried to assess the coronary disease progression in the clinical, surgical, and angioplasty groups in the LAD, LCX, and RCA arteries in diabetic (n=138) and nondiabetic patients (n=254). A total of 392 subjects randomly assigned to CABG (n=136), 57 diabetic and 79 non diabetic, PCI (n=146),42 diabetic and 104 non diabetic or medical treatment(n=110) 38 diabetic and 72 non diabetic Also, we analyzed the relation of the rate of progression with morbidity and the need for an additional intervention. Results: No significant differences in relation to age, sex, hypertension, smoking, or lipid disorders were observed between the groups. Furthermore, no differences concerning CAD progression were shown when diabetic and nondiabetic subject were compared. However, when the type of treatment was stratified, the surgery group had less progression in the diabetic group (69.7% p =0.014). On the other hand, more progression in the PCI group was observed in RCA (64.3 %) and LAD (71.5%) territories in diabetic group (p=0.047; p=0.024). No relation was found between progression and the rate of events in both groups. Conclusion: Diabetes was not associated with greater progression of CAD in patients with stable CAD and preserved ventricular function during 5-year follow-up. However, the diabetic patients who underwent PCI had more progression of CAD compared with nondiabetic subjects in RCA and LAD territories.The surgery group shown less progression of the disease in the diabetic group.

Existe a hipótese, dentro da medicina periodontal, de uma possível relação entre doença periodontal e doenças cardíacas. Talvez a doença periodontal possa agir como um fator desencadeante para o desenvolvimento da doença cardiovascular. Vinte e oito pacientes portadores de aterosclerose e periodontite crônica, submetidos à intervenção cirúrgica de revascularização cardíaca e endarterectomia coronariana, participaram do estudo, cujo objetivo foi avaliar nas placas de ateroma de artérias coronárias a presença dos periodontopatógenos do complexo vermelho: Porphyromonas gingivalis, Tannerella forsythia e Treponema denticola. O DNA genômico foi extraídos das amostras de ateromas e se constatou a presença das bactérias através da reação em cadeia da polimerase (PCR). Detectou-se nas 28 amostras de ateroma: P. gingivalis em 50%, T. forsythia em 7,1% e T. denticola em 3,6% respectivamente. Estes resultados ajudam a defender a hipótese de que a doença periodontal pode ser um dos muitos fatores envolvidos com o desenvolvimento da doença cardiovascular, sendo mais um motivo para ser precocemente diagnosticada, prevenida e tratada. / In the field of periodontal medicine there is the hypothesis of a possible connection between periodontal diseases and heart diseases. Maybe the periodontal disease may work as a triggering factor in the development of periodontal of cardiovascular diseases. Twenty-eight patients of atherosclerosis and cronical periodontitis patients were subjected to surgical intervention for cardiac revascularization and coronary endarterectomy, have made part of the study, whose objective was to evaluate the presence of periodontopathogens of the red complex in the atheroma platelets: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Genomic DNA was extracted from atheroma samples, and the presence of bacteria was stated through polymerase chain reaction (PCR). In the 28 samples of atheroma were detected: P. gingivalis at 50%, T. forsythia at 7.1% and T. denticola at 3.6% respectively. These results help to sponsor the hypothesis that the periodontal disease can be one of several factors involved in the development of cardiovascular disease, being this another reason for its early diagnosis, prevention and treatment.

Estudos têm reportado o impacto periodontite na aterosclerose. Neste estudo verificamos a associação determinando alguns marcadores de risco para aterosclerose, e verificarmos a influência do tratamento periodontal sobre esses marcadores. Quarenta pacientes com periodontite e 40 sem periodontite foram incluídos. Colesterol Total, e frações, triacilglicerol (TG), níveis de citocinas, anticorpos anti-oxLDL, proteína C Reativa (PCR), contagem de leucócitos e neutrófilos, e índice de refração foram investigados. Interleucina (IL)-6, -8 e PCR, anticorpos anti-oxLDL, TG e contagem de leucócitos e neutrófilos foram maiores em pacientes com periodontite. Os pacientes com periodontite passaram por tratamento periodontal. Novas coletas foram feitas após 3, 6 e 12 meses após o tratamento. Um ano após o tratamento, as concentrações de TG, IL-6, -8, PCR, contagem de leucócitos e neutrófilos e anticorpos anti-oxLDL foram significantemente menores. Nossos resultados confirmam que o tratamento periodontal induz mudanças sistêmicas em vários marcadores de risco para aterosclerose. / Studies have reported the impact of periodontitis on atherosclerosis. In this study we verify the association by determining some of risk markers for atherosclerosis, and we verify the effect of periodontal treatment on these risk markers. Forty patients with chronic periodontitis and 40 without periodontal disease were included. Total cholesterol and fractions, triacyglycerol (TG), levels of cytokines, antibodies anti-oxLDL, C reactive protein (CRP), leukocyte and neutrophils count, and the non-linear index were investigated. Interleukin (IL)-6,-8 and CRP, antibodies anti-oxLDL, TG and leukocyte and neutrophils counts were higher in periodontitis patients. The patients with periodontitis underwent periodontal treatment. Additional samples were collected after 3, 6 and 12 months after treatment. One year after the treatment, TG, IL-6,-8, CRP, Leukocyte and neutrophils counts, anti-oxLDL antibody were significantly lower. Our results confirmed that the periodontal treatment induces systemic changes in several markers the risk for atherosclerosis.

Introdução: Os fitoesteróis (FE) são reconhecidos por reduzirem a concentração plasmática de LDL-colesterol, sendo importantes coadjuvantes no tratamento da hipercolesterolemia moderada. Entretanto, estudos publicados recentemente demonstram resultados conflitantes em relação à eficiência dos FE na prevenção da aterosclerose. Além disso, algumas investigações evidenciaram que o aumento da concentração plasmática de FE está positivamente relacionado ao risco de desenvolvimento de aterosclerose. Com a finalidade de elucidar a sua ação sobre esses parâmetros, o objetivo deste estudo foi avaliar os efeitos da suplementação de FE no desenvolvimento da aterosclerose em camundongos com ablação gênica para o receptor de LDL (LDLr-KO). Métodos: Os animais foram alimentados durante 16 semanas, com dieta rica em gordura (40% do valor calórico total da dieta), suplementada (grupo FE; 2%, n=10) ou não (Controle; n=10) com FE. Foram avaliadas as concentrações plasmáticas e hepáticas de colesterol, triglicérides, FE (beta-sitosterol, campesterol e latosterol). Na aorta dos animais, determinaram-se as concentrações de colesterol total, colesterol livre e éster e FE, além do infiltrado de macrófagos e infiltrado de lípides. Nos macrófagos do peritôneo dos animais, os quais assemelham-se aos presentes na artéria, avaliou-se a expressão de RNA mensageiro dos genes envolvidos no efluxo e influxo de colesterol (ABCA1, ABCG1, LOX1 e CD36). Também determinou-se as concentrações de FE no intestino e baço dos animais. Resultados: Conforme esperado, o consumo de FE induziu elevação plasmática dos principais FE, campesterol e de beta-sitosterol, reduzindo a concentração de colesterol no plasma. Houve aumento nas concentrações hepáticas de triglicérides e FE, entretanto, não foram observadas diferenças entre os grupos nas expressões de RNA mensageiro de genes lipolíticos (CPT, PPAR alfa) e lipogênicos (SREBP1-c, MTP, LXR e PPAR gamma) no fígado. Não houve, também, alteração no SREBP2, gene relacionado à síntese de colesterol. O conteúdo de colesterol total na artéria foi menor nos animais do grupo FE, não diferindo entre as formas livre e éster. As concentrações de FE na artéria foram iguais entre os grupos. A área de lesão no grupo FE foi menor em relação ao grupo-controle. A suplementação com FE induziu redução na expressão de RNA mensageiro de ABCG1, não interferindo na expressão dos outros genes estudados na artéria. Conclusão: Os achados deste estudo demonstram que a elevação de FE no plasma não induziu o seu acúmulo na parede da artéria e preveniu o desenvolvimento da aterosclerose / Introduction: The plasma cholesterol-reducing effect of hytosterols (PS) is well recognized and they are considered important adjuncts in the treatment of moderate hypercholesterolemia. However, recent studies have shown conflicting results regarding the efficiency of PS in the prevention of atherosclerosis. In addition, some studies showed that the increase in plasma PS concentration is positively correlated to the risk of atherosclerosis. In order to elucidate its action on these parameters, the objective of this study was to evaluate the effects of PS supplementation in the development of atherosclerosis in LDL receptor knock-out mice (LDLr -KO). Methods: The animals were fed during 16 weeks with high fat diet (40 % of calories as fat), supplemented (PS group, 2%, n = 10) or not (Control, n = 10) with PS. Plasma and liver concentrations of cholesterol, triglycerides, PS (beta - sitosterol, campesterol and lathosterol) were evaluated. In the aorta of the animals, the concentrations of total cholesterol, free cholesterol, cholesterol ester and PS, besides macrophage and lipids infiltration were determined. The mRNA expression of genes involved in cholesterol efflux and influx (ABCA1, ABCG1, LOX1 and CD36) were evaluated, in peritoneum macrophage, which resemble those present in the artery. It was also determined the intestine and spleen PS concentrations from the animals of both groups. Results: As expected, PS supplementation induced increasing plasma concentration of the main PS, campesterol and beta -sitosterol and reducing cholesterol plasma concentration. It was observed an increase so intestine and spleen PS concentrations. There was an increase in hepatic triglyceride concentrations and PS, however, no differences were observed between the groups of hepatic mRNA expression of lipolytic (CPT, PPARalfa) and lipogenic genes (SREBP1c, MTP, CPT, LXR, and PPAR gamma). There was no difference on SREBP2, gene related to cholesterol synthesis. The content of total cholesterol in the artery was lower in PS group animals however did not differ between the free and ester forms. Artery PS concentrations did not differ between groups. The lesion area in the PS group was lower than in the control group. PS supplementation induced reduction in mRNA expression of ABCG1, not affecting the expression of other genes studied in artery. Conclusion: The findings of this study demonstrate that the elevation of plasma PS concentration did not induce its accumulation in the arterial wall and prevented the development of atherosclerosis