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Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p

In recent decades, complex and exquisite pathways involved in the endoplasmic reticulum (ER) and inflammatory stress responses have been demonstrated to participate in the development and progression of numerous diseases, among them diabetes mellitus (DM). In those pathways, several players participate in both, reflecting a complicated interplay between ER and inflammatory stress. In DM, ER and inflammatory stress are involved in both the pathogenesis of the loss of glycemic control and the development of degenerative complications. Furthermore, hyperglycemia increases the generation of advanced glycation end products (AGEs), which in turn refeed ER and inflammatory stress, contributing to worsening glycemic homeostasis and to accelerating the development of DM complications. In this review, we present the current knowledge regarding AGEs-induced and ER/inflammation-mediated regulation of the expression of GLUT4 (solute carrier family 2, facilitated glucose transporter member 4), as a marker of glycemic homeostasis and of cardiovascular disease (CVD) development/progression, as a leading cause of morbidity and mortality in DM.

Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p

Introduction: Cardiovascular disease has become a significant condition affecting human health. Increased arterial stiffness is a leading stage in the occurrence and development of many cardiovascular diseases. Objective: To observe the effect of different acute exercise programs on arterial stiffness of healthy young people under the same amount of exercise. Methods: We selected 16 healthy boys to conduct a blank control test, continuous exercise test, and intermittent exercise. They were divided into blank schemes. Car plan and running plan. Arterial stiffness was repeatedly measured immediately after exercise and 40 minutes after the end. Results: In the three exercise intervention experiments, the heart-ankle vascular index decreased significantly immediately after exercise. After 60 minutes of rest, the heart-ankle vascular index rebounded. Conclusion: Physical exercise can significantly reduce arterial stiffness. Changing the training intensity in sports with the same target heart rate does not affect arterial stiffness. Level of evidence II; Therapeutic studies - investigation of treatment results. RESUMO Introdução: Doenças cardiovasculares tem se tornado uma condição importante afetando a saúde humana. O aumento da rigidez arterial é uma etapa determinante na ocorrência e no desenvolvimento de muitas doenças cardiovasculares. Objetivo: Observar o efeito de diferentes programas de exercício intenso na rigidez arterial de jovens saudáveis praticando a mesma quantidade de exercício. Métodos: Selecionamos 16 rapazes saudáveis para conduzir um ensaio em branco, testes com exercícios e exercícios intermitentes. Os indivíduos foram divididos em amostras em branco, plano xxx e plano de corrida. A rigidez arterial foi medida repetidas vezes imediatamente após o exercício e 40 minutos após. Resultados: nos três experimentos de intervenção, o índice vascular cardíaco-tornozelo diminuiu consideravelmente imediatamente após o exercício. Após 60 minutos de descanso, o índice vascular cardíaco-tornozelo se recuperou. Conclusão: Exercícios físicos podem reduzir a rigidez arterial de forma considerável. Modificar a intensidade do treino nos esportes com a mesma frequência cardíaca alvo não afeta a rigidez arterial. Nível de evidência II; Estudos terapêuticos – investigação de resultados de tratamento. RESUMEN Introducción: Enfermedades cardiovasculares se han convertido en una condición importante que afecta la salud humana. El aumento de la rigidez arterial es una etapa determinante en la ocurrencia y en el desarrollo de muchas enfermedades cardiovasculares. Objetivo: Observar el efecto de diferentes programas de ejercicio intenso en la rigidez arterial de jóvenes saludables practicando la misma cantidad de ejercicio. Métodos: Seleccionamos 16 muchachos saludables para conducir un ensayo en blanco, pruebas con ejercicios y ejercicios intermitentes. Se dividieron los individuos en blanco de muestra, plan de xxx y plan de carrera. Se midió la rigidez arterial repetidas veces inmediatamente tras el ejercicio y 40 minutos después. Resultados: En los tres experimentos de intervención, el índice vascular cardiaco-tobillo disminuyó considerablemente inmediatamente tras el ejercicio. Tras 60 minutos de descanso, el índice vascular cardiaco-tobillo se recuperó. Conclusión: Ejercicios físicos pueden reducir la rigidez arterial de forma considerable. Cambiar la intensidad del entrenamiento en los deportes con la misma frecuencia cardiaca-blanco no afecta la rigidez arterial. Nivel de evidencia II; Estudios terapéuticos – investigación de resultados de tratamiento.

Orientadores: Admar Costa de Oliveira, Eder C. R. Quintão Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos Resumo: O transporte reverso de colesterol é um dos mecanismos que podem explicar a relação inversa entre os níveis plasmáticos de lipoproteínas de alta densidade (HDL) e a incidência de doença aterosclerótica no homem. Por esse processo, o colesterol dos tecidos periféricos, inclusive da parede arterial, é removido das membranas celulares pelas HDL, esterificado pela lecitina colesterol-aciltransferase e, posteriormente, captado pelo figado (transporte reverso direto de colesterol). O colesterol celular também é removido por via indireta, ou seja, pela transferência do-colesterol esterificado das HDL para as lipoproteínas que contém apo B (lipoproteínas de muito baixa e baixa densidade, respectivamente VLDL e LDL) as quais são captadas por receptores específicos hepáticos. Essa etapa é mediada pela proteína de transferência de éster de colesterol.(CETP). As lipoproteínas de baixa densidade são quantitativamente as maIS importantes lipoproteínas carreadoras de colesterol. Elas estão positivamente associadas ao desenvolvimento da aterosclerose e, desta forma, altas concentrações de LDL plasmáticas e/ou modificações químicas destas lipoproteínas, como a oxidação, são condições relacionadas diretamente ao aumento da incidência da doença aterosclerótica. Com o objetivo de avaliar a atividade da CETP frente a modificações químicas induzi das artificialmente nas LDL, foram feitos experimentos de medida de transferência de éster de colesterol radioativamente marcado entre as lipoproteínas. Lipoproteínas obtidas a partir de "pool" de plasma de indivíduos nonnais, foram modificadas "in vitro" por acetilação ou oxidação e foram incubadas com HDL2 e HDL3 previamente marcadas com éster de colesterol radioativo, na presença de CETP contida na fração do plasma de d> 1,21g1rnL. Após vários períodos de incubação, as lipoproteínas foram reisoladas por precipitação das LDL com sulfato de dextrana/MgCh e a radioatividade medida no sobrenadante. Os resultados obtidos mostraram diminuição média significativa na transferência de éster de colesterol das subpopulações de HDL (HDL2 e HDL3 em conjunto) para as LDL modificadas por acetilação (p=O,OOOI) ou por oxidação (p=O,OO88), quando comparadas às respectivas LDL normais. A diminuição encontrada na porcentagem de transferência das HDL para a LDL acetilada foi de 1,8 vezes e para a LDL oxidada foi de 1,5 vezes em relação às respectivas LDL normais. A via inversa, ou seja,. transporte de éter de colesterol da LDL oxidada para as subpopulações de HDL, apresentou um aumento médio significativo (p=O,OOO5) de cerca de 2 vezes, quando comparado à LDL normal. A diminuição da transferência de colesterol esterificado (CO) das HDL para as LDL modificadas contribui para que estas lipoproteínas aterogênicas ganhem menos colesterol do que as LDL não modificadas. Por outro lado, a maior transferência de colesteril-oleato das LDL oxidadas para as HDL, resulta na redistribuição do colesterol oxidado para uma fração lipoprotéica antiaterogênica. Como o destino metabólico das LDL modificadas é a captação por macrófagos na parede arterial (ateroma) e o das LDL e das HDL normais é o hepatócito (excreção de colesterol do corpo), os resultados mostraram que a CETP favoreceu a redistribuição do colesterol plasmático para as lipoproteínas íntegras, antiaterogênicas, indicando um possível papel antiaterogênico da CETP o que também foi recentemente descrito em um estudo populacional Abstract: Reverse transport of cholesterol is a mechanism that possibly explains an inverse correlation between high density lipoprotein (HDL) levels and the incidence of atherosclerosis. In this process peripheral cholesterol tissue, including that of the arterial wall, is removed from cellular membranes by HDL, esterified by lecithin-cholesterol-acyltransferase and thereafter taken up by the liver (direct reverse transport of cholesterol). Cellular cholesterol is also transported by an indirect way, that is, by means of the transfer of esterified cholesterol from HDL to the lipoproteins that contain apo B (low and very low density lipoproteins, respectively, VLDL and LDL) and that is intemalized by specific hepatic receptors. Thisstep is mediated by the cholesterol ester transfer protein (CETP). Low density lipoproteins quantitatively are the most important carriers of cholesterol. They are positively associated with the development of atherosclerosis, and in this way, high concentrations of plasma LDL and chemical modification of these lipoproteins are conditions direct1y related to atherogenesis. In order to study the activity of CETP on LDL particles chemically modified, experiments were made to measure the transfer of radioactive cholesteryl ester between lipoproteins. Lipoproteins obtained from the plasma pool of normal individuaIs were modified "in vitro" by acetylation or oxidation, and were incubated with HDL2 and HDL3 containing radioactive cholesteryl ester in the presence of CETP from plasma fraction of d > 1.2 1 g/rnL. After various incubation periods, the lipoproteins were isolated again by pr.ecipitation of LDL with dextran sulfate/MgCh and the radioactivity measured in the supematant. The results obtained showed a significant average diminution in the transfer of cholesteryl ester from HDL2 and HDL3 to the LDL modified by acetylation or by oxidation, when compared to the nonnal LDL. In the inverse direction that is, the transport of oxidized LDL cholesteryl ester to the subpopulations of HDL presented a significant average increase, when compared to nonnal LDL. The diminished transfer rate of esterified cholesterol (CO) from HDL to the modified LDL brings about a significantly smaller enrichment of the latter with cholesterol. On the other hand, the faster transfer rate of CO from oxidized LDL to HDL lessens the atherogenic pot~ntial of the fonner lipoproteins. Taking into account that modified LDL is bound to accumulate into the arterial wall whereas nonnal LDL and HDL are preferentially taken up by the hepatocyte, the data suggest that CETP plays a benefical role favoring the excretion of cholesterol from the body, which is in agreement with a recent epidemiological study suggesting an antiatherogenic role of CETP Doutorado Doutor em Ciência da Nutrição

Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

Resumo A principal causa de óbito na contemporaneidade são as doenças cardiovasculares. Arteriosclerose, aterosclerose, arteriolosclerose e arteriosclerose de Monckeberg são termos frequentemente utilizados como sinônimos, mas traduzem alterações distintas. O objetivo desta revisão foi discutir os conceitos de arteriosclerose, aterosclerose, arteriolosclerose e esclerose calcificante da média de Monckeberg. O termo arteriosclerose é considerado mais genérico, significando o enrijecimento e a consequente perda de elasticidade da parede arterial, abarcando os demais tipos. A aterosclerose é uma doença inflamatória secundária a lesões na camada íntima, que tem como principal complicação obstrução crônica e aguda do lúmen arterial. A arteriolosclerose se refere ao espessamento das arteríolas, particularmente relacionada à hipertensão arterial sistêmica. Já a esclerose calcificante da média de Monckeberg designa a calcificação, não obstrutiva, da lâmina elástica interna ou da túnica média de artérias musculares. As calcificações vasculares, que incluem lesões ateroscleróticas e a esclerose calcificante da média de Monckeberg, vêm sendo estudadas como um fator de risco para a morbimortalidade cardiovascular. Abstract Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.

We study the advection of blood particles in the carotid bifurcation, a site that is prone to plaque development. Previously, it has been shown that chaotic advection can take place in blood flows with diseases. Here, we show that even in a healthy scenario, chaotic advection can take place. To understand how the particle dynamics is affected by the emergence and growth of a plaque, we study the carotid bifurcation in three cases: a healthy bifurcation, a bifurcation with a mild stenosis, and the another with a severe stenosis. The result is non-intuitive: there is less chaos for the mild stenosis case even when compared to the healthy, non-stenosed, bifurcation. This happens because the partial obstruction of the mild stenosis generates a symmetry in the flow that does not exist for the healthy condition. For the severe stenosis, there is more irregular motion and more particle trapping as expected.

Background The aim of this study was to determine the impact of metabolic syndrome (MetS) on the morphology of carotid plaques, as evaluated using duplex ultrasound (DUS) with computer-assisted analysis. Methods In this cross-sectional observational study, we analyzed 148 carotid artery plaques in asymptomatic patients. Data were obtained via clinical and laboratory examinations, and DUS was performed by a single operator. All plaques were scanned in a longitudinal fashion, and the best segment was selected, recorded, and evaluated using dedicated software. The main software-based analyses included gray-scale median (GSM) measurements and carotid plaque morphology histograms. Results MetS was identified in 51.8% of patients. Comparisons of patients with MetS and patients without MetS indicated that the former patients used more classes of antihypertensive drugs (2.49 vs. 1.93; P = 0.004) and were treated with statins for a longer period (71.08 vs. 49.17 months; P = 0.003). Most patients of both types exhibited moderate carotid artery stenosis ranging from 50% to 69% ( n = 62; 37.3%), and MetS was not associated with an increased prevalence of severe carotid artery stenosis. The mean GSM was greater in the MetS group than in the non-MetS group (74.18 vs. 61.63; P = 0.012). The histogram analysis revealed that there were lower quantities of blood and fat (2.91 vs. 3.88; P = 0.006; 10.21 vs. 15.08; P = 0.004, respectively) and more fibrous tissue (19.93 vs. 14.55; P = 0.015) in the carotid plaques of patients with MetS than in the carotid plaques of patients without MetS. Conclusions The present study demonstrated that MetS did not affect the stenosis grade or did it lead to unstable carotid plaques.

The inflammasome is responsible for maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) contributing to the inflammatory process in atherosclerosis. It is shown here that an electronegative low-density lipoprotein [LDL (-)] apoB-100 mimetic peptide can activate the transcriptional and posttranslational signs needed for complete inflammasome activation. This peptide, named p2C7, can activate the Toll-like receptor 4 (TLR4) that induces NF-κB activation and the transcription of inflammasome components. After blocking TLR4 with a neutralizing antibody, inflammasome component (NLRP3, CASP1, and ASC) and IL1b and IL18 gene downregulation occurred in human-derived macrophages stimulated with p2C7 or LDL (-). Moreover, the posttranslational signal was activated by the interaction between p2C7 and the lectin-type oxidized LDL receptor 1 (LOX-1), as demonstrated by the induction of caspase-1 cleavage in macrophages. The blockage of either TLR4 or LOX-1 decreased IL-1β and IL-18 secretion by human-derived macrophages as both pathways are necessary for complete inflammasome activation. These findings suggest a mechanism by which macrophages transduce the pro-inflammatory signal provided by LDL (-) ApoB-100 and its mimetic peptides to activate the inflammasome protein complex what may be relevant for the inflammatory process in atherosclerosis.

Arteries, like soft biological tissues in general, have an internal structure and a complex organization on several scales. Some phenomena alter this microstructure inducing a modification of their response at the same level of stimuli and therefore their macroscopic behavior. Among these phenomena, there may be mentioned arteriosclerosis, a natural process which is characterized by thickening and lowest deformability of the arterial wall. The arterial wall has stiffened. This stiffening is due in part to the remodeling corresponding to a modification of structure involving synthesis of new constituents with a different organization or reorganization of existing ones. We can also mention atherosclerosis, a pathology resulting in accumulation of lipids, carbohydrates, adipose tissue, etc. creating a plaque called atheroma at the inner wall of the artery. This pathology accelerates arteriosclerosis and subsequently modifies the microstructure by remodeling. The optimization of therapeutic techniques applied to the diseases of the arterial system requires the analysis of the artery considered as a mechanical system. Thus, mathematical modelling of its mechanical behavior is imperative. Given the complexity of its microstructure, we opted for a representation of its behavior in the context of Eringen micromorphic media and more particularly in the context of microdilatation media.The artery, in normal operating conditions, is subjected to small elastic deformations. The solution of field equations for analysing the state of stress and deformation induced by an external stimulus can generally be obtained only numerically. Due to the complexity of the behaviour model, we had to develop a dedicated tool. It is based on a clever coupling of the boundary element method and a collocation point method. The digital tool developed has been validated on a number of simple cases allowing a comparison of numerical and analytical solutions. The analysis of the artery as a homogeneous microdilatation medium is undertaken initially. Then, motivated by the observation of the layered structure of the artery with different mechanical properties, the analysis continues by considering the medium as non-homogeneous. The work was then extended to the study of arteriosclerosis by first simulating the modification of the deformability by a modification of the microstructural characteristics then by the insertion of inert inclusions. An in-depth study of the impact of such areas with different size and position in the arterial wall is conducted. Finally, atherosclerosis and angioplasty are approached by considering a rigid atheroma plaque. The results obtained highlight some clinical observations. In particular, we can mention the remodelling process induced by the local degeneration of the mechanical properties of the artery or by the stent placement whose clinical utility is no longer to be demonstrated. This work should be continued by the effective identification of the microstructural parameters of the artery and by the optimization of the mechanical properties of stents to localize the remodeling area. It will also be necessary to take into account the global anisotropy of the artery., Les artères, comme les tissus biologiques mous en général, possèdent une structure interne et une organisation complexe sur des échelles difficilement différenciables. Certains phénomènes viennent altérer cette microstructure induisant ainsi une modification de leur réponse au même niveau de stimuli et donc de leur comportement macroscopique. On peut citer l’artériosclérose qui est un processus naturel qui se caractérise par un épaississement et une moins bonne déformabilité de la paroi artérielle. On dit alors que la paroi artérielle s’est rigidifiée. Celle-ci est due en partie au remodelage correspondant à une modification de structure intervenant par synthèse de nouveaux constituants avec une organisation différente ou par réorganisation de ceux qui sont existants. On peut aussi mentionner l’athérosclérose, une pathologie se traduisant par l’accumulation de lipides, glucides, tissus adipeux, etc. créant une plaque appelée athérome au niveau de la paroi interne de l’artère. Celle-ci vient accélérer l’artériosclérose et par suite modifier la microstructure par remodelage. L’optimisation des techniques thérapeutiques appliquées à certaines maladies du système artériel nécessite l’analyse de l’artère considérée comme un système mécanique. De ce fait, la modélisation mathématique de son comportement mécanique est impérative. Compte tenu de la complexité de sa microstructure, nous avons opté pour une représentation de son comportement dans le cadre des milieux micromorphiques de Eringen et plus particulièrement dans le cadre des milieux à microdilatation. On conçoit aisément que l’artère est sollicitée en régime de fonctionnement normal dans le domaine de petites déformations élastiques. La solution des équations de champ permettant d’analyser l’état de contrainte et de déformation induit par un stimulus extérieur ne peut en général être obtenue que numériquement. Du fait de la complexité du modèle de comportement, nous avons dû développer un outil numérique spécifiquement dédié. Cet outil est basé sur un couplage astucieux de la méthode des éléments de frontières et d’une méthode sans maillage de collocation par points. Cet outil numérique a été validé sur un nombre de cas simples permettant une comparaison des solutions numériques et analytiques. L’analyse de l’artère comme un milieu à microdilatation homogène est entrepris dans un premier temps. Puis, motivée par l’observation de la structure en couches de l’artère dont les propriétés mécaniques sont différentes, l’analyse se poursuit en considérant le milieu comme non homogène. Le travail a ensuite été étendu à l’étude de l’artériosclérose en simulant en premier lieu la modification de la déformabilité par une modification des caractéristiques microstructurales puis par l’insertion d’inclusions inertes. Une étude approfondie sur l’impact que peuvent avoir de telles zones en fonction de leur taille et leur position dans la paroi artérielle est menée. Enfin, l’athérosclérose et l’angioplastie sont abordées par la prise en compte d’une plaque d’athérome rigide. Les résultats obtenus ont déjà permis d’éclairer certaines observations cliniques. On peut en particulier mentionner le processus de remodelage induit par la dégénérescence locale des propriétés mécaniques de l’artère ainsi que par la pose d’un stent dont l’utilité clinique n’est plus à démontrer. Ce travail devrait être poursuivi par l’identification effective des paramètres microstructuraux et par l’optimisation des propriétés mécaniques de stents pour une localisation de la zone de remodelage. Il sera aussi nécessaire de prendre en compte l’anisotropie de l’artère.

Arteries, like soft biological tissues in general, have an internal structure and a complex organization on several scales. Some phenomena alter this microstructure inducing a modification of their response at the same level of stimuli and therefore their macroscopic behavior. Among these phenomena, there may be mentioned arteriosclerosis, a natural process which is characterized by thickening and lowest deformability of the arterial wall. The arterial wall has stiffened. This stiffening is due in part to the remodeling corresponding to a modification of structure involving synthesis of new constituents with a different organization or reorganization of existing ones. We can also mention atherosclerosis, a pathology resulting in accumulation of lipids, carbohydrates, adipose tissue, etc. creating a plaque called atheroma at the inner wall of the artery. This pathology accelerates arteriosclerosis and subsequently modifies the microstructure by remodeling. The optimization of therapeutic techniques applied to the diseases of the arterial system requires the analysis of the artery considered as a mechanical system. Thus, mathematical modelling of its mechanical behavior is imperative. Given the complexity of its microstructure, we opted for a representation of its behavior in the context of Eringen micromorphic media and more particularly in the context of microdilatation media.The artery, in normal operating conditions, is subjected to small elastic deformations. The solution of field equations for analysing the state of stress and deformation induced by an external stimulus can generally be obtained only numerically. Due to the complexity of the behaviour model, we had to develop a dedicated tool. It is based on a clever coupling of the boundary element method and a collocation point method. The digital tool developed has been validated on a number of simple cases allowing a comparison of numerical and analytical solutions. The analysis of the artery as a homogeneous microdilatation medium is undertaken initially. Then, motivated by the observation of the layered structure of the artery with different mechanical properties, the analysis continues by considering the medium as non-homogeneous. The work was then extended to the study of arteriosclerosis by first simulating the modification of the deformability by a modification of the microstructural characteristics then by the insertion of inert inclusions. An in-depth study of the impact of such areas with different size and position in the arterial wall is conducted. Finally, atherosclerosis and angioplasty are approached by considering a rigid atheroma plaque. The results obtained highlight some clinical observations. In particular, we can mention the remodelling process induced by the local degeneration of the mechanical properties of the artery or by the stent placement whose clinical utility is no longer to be demonstrated. This work should be continued by the effective identification of the microstructural parameters of the artery and by the optimization of the mechanical properties of stents to localize the remodeling area. It will also be necessary to take into account the global anisotropy of the artery.; Les artères, comme les tissus biologiques mous en général, possèdent une structure interne et une organisation complexe sur des échelles difficilement différenciables. Certains phénomènes viennent altérer cette microstructure induisant ainsi une modification de leur réponse au même niveau de stimuli et donc de leur comportement macroscopique. On peut citer l’artériosclérose qui est un processus naturel qui se caractérise par un épaississement et une moins bonne déformabilité de la paroi artérielle. On dit alors que la paroi artérielle s’est rigidifiée. Celle-ci est due en partie au remodelage correspondant à une modification de structure intervenant par synthèse de nouveaux constituants avec une organisation différente ou par réorganisation de ceux qui sont existants. On peut aussi mentionner l’athérosclérose, une pathologie se traduisant par l’accumulation de lipides, glucides, tissus adipeux, etc. créant une plaque appelée athérome au niveau de la paroi interne de l’artère. Celle-ci vient accélérer l’artériosclérose et par suite modifier la microstructure par remodelage. L’optimisation des techniques thérapeutiques appliquées à certaines maladies du système artériel nécessite l’analyse de l’artère considérée comme un système mécanique. De ce fait, la modélisation mathématique de son comportement mécanique est impérative. Compte tenu de la complexité de sa microstructure, nous avons opté pour une représentation de son comportement dans le cadre des milieux micromorphiques de Eringen et plus particulièrement dans le cadre des milieux à microdilatation. On conçoit aisément que l’artère est sollicitée en régime de fonctionnement normal dans le domaine de petites déformations élastiques. La solution des équations de champ permettant d’analyser l’état de contrainte et de déformation induit par un stimulus extérieur ne peut en général être obtenue que numériquement. Du fait de la complexité du modèle de comportement, nous avons dû développer un outil numérique spécifiquement dédié. Cet outil est basé sur un couplage astucieux de la méthode des éléments de frontières et d’une méthode sans maillage de collocation par points. Cet outil numérique a été validé sur un nombre de cas simples permettant une comparaison des solutions numériques et analytiques. L’analyse de l’artère comme un milieu à microdilatation homogène est entrepris dans un premier temps. Puis, motivée par l’observation de la structure en couches de l’artère dont les propriétés mécaniques sont différentes, l’analyse se poursuit en considérant le milieu comme non homogène. Le travail a ensuite été étendu à l’étude de l’artériosclérose en simulant en premier lieu la modification de la déformabilité par une modification des caractéristiques microstructurales puis par l’insertion d’inclusions inertes. Une étude approfondie sur l’impact que peuvent avoir de telles zones en fonction de leur taille et leur position dans la paroi artérielle est menée. Enfin, l’athérosclérose et l’angioplastie sont abordées par la prise en compte d’une plaque d’athérome rigide. Les résultats obtenus ont déjà permis d’éclairer certaines observations cliniques. On peut en particulier mentionner le processus de remodelage induit par la dégénérescence locale des propriétés mécaniques de l’artère ainsi que par la pose d’un stent dont l’utilité clinique n’est plus à démontrer. Ce travail devrait être poursuivi par l’identification effective des paramètres microstructuraux et par l’optimisation des propriétés mécaniques de stents pour une localisation de la zone de remodelage. Il sera aussi nécessaire de prendre en compte l’anisotropie de l’artère.

Background and aims Regular intake of phytosterols (PS) is proven to dose-dependently lower LDL-cholesterol (LDL-C). Whether PS consumption can also impact low-grade inflammation is unclear. Considering the low feasibility of outcomes studies involving PS consumption, investigation of surrogate markers of atherosclerosis represents a valuable approach. This study assessed the anti-inflammatory effect of PS consumption, according to inflammatory biomarkers, mainly C-reactive protein (CRP). Methods and results A systematic search of Medline, Cab Abstracts, and Food Science & Technology Abstracts was conducted through January 2015. Our study selection included randomized controlled trials (RCT), involving intake of PS-enriched foods as active treatment, and measurement of plasma inflammatory biomarkers. Random-effects meta-analyses were performed using average baseline and end-of-intervention concentrations and control-adjusted absolute changes in CRP and blood lipids. There were 20 eligible RCTs including a total of 1308 subjects. The absolute change of plasma CRP levels with PS consumption was −0.10 mg/L (95%CI -0.26; 0.05), a non-significant change, and heterogeneity had borderline significance (I 2 = 29.1; p-value = 0.073). The absolute reduction of LDL-C was −14.3 mg/dL (95%CI -17.3; -11.3). Meta-regression analyses showed that both the dose and duration of PS intake significantly influenced the absolute changes in plasma CRP (β = −0.35, p = 0.0255 and β = −0.03, p = 0.0209, respectively). Conclusions In this meta-analysis, regular intake of PS-enriched foods did not significantly change CRP, whilst LDL-C concentrations were significantly reduced. Further studies with higher PS doses may provide more definite conclusions on a potential anti-inflammatory effect of PS intake.

Background-—Emotional disorders are risk factors for atherosclerosis and consequent cardiovascular disease. However, it is not clear whether emotional symptoms (ESs) have direct effects on cardiovascular disease. The aim of the present study is to investigate the effects of early ESs on carotid atherosclerosis in young adults. Methods and Results-—We tested the association between expression of ESs at 11 and 15 years of age and carotid intima-media thickness at 18 years of age in the 1993 Pelotas Birth Cohort (N=5249, n=4336 with complete mental health data). ESs were assessed using the Strengths and Difficulties Questionnaire. Propensity score weighting procedure was run using generalized boosted regression model to adjust for potential confounding between exposure and outcome. We also tested whether traditional cardiovascular risk factors could mediate this relationship. Adjusted high expression of ESs, both at 11 and 15 years of age, led to mean increases in carotid intima-media thickness of 1.84 and 2.58 lm, respectively, at 18 years of age (both P

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2019 Submitted by Sofia Amador (sofiamador@fm.ul.pt) on 2020-04-20T13:44:08Z No. of bitstreams: 1 FilipeAPatricio.pdf: 1860722 bytes, checksum: 295190afe54a9b96e7ea64b4928b062a (MD5) Made available in DSpace on 2020-04-20T17:05:37Z (GMT). No. of bitstreams: 1 FilipeAPatricio.pdf: 1860722 bytes, checksum: 295190afe54a9b96e7ea64b4928b062a (MD5) Previous issue date: 2019

Mestrado em Engenharia Biomédica Submitted by Maria da Luz Antunes (mluz.antunes@estesl.ipl.pt) on 2019-12-12T10:19:44Z No. of bitstreams: 1 Deteção automática e caracterização da placa aterosclerótica através da imagem ultrassonográfica.pdf: 1997002 bytes, checksum: 059c3cdd607cbdc2200fb9d949069afd (MD5) Made available in DSpace on 2019-12-12T10:19:44Z (GMT). No. of bitstreams: 1 Deteção automática e caracterização da placa aterosclerótica através da imagem ultrassonográfica.pdf: 1997002 bytes, checksum: 059c3cdd607cbdc2200fb9d949069afd (MD5) Previous issue date: 2018-12 N/A

Leukocyte migration is essential for the function of the immune system. Their recruitment from the vessels to the tissues involves sequential molecular interactions between leukocytes and endothelial cells (ECs). Many adhesion molecules involved in this process have already been described. However, additional molecules may be important in this interaction, and here we explore the potential role for CD100 and plexins in monocyte-EC binding. CD100 was shown to be involved in platelet-endothelial cell interaction, an important step in atherogenesis and thrombus formation. In a recent work we have described CD100 expression in monocytes and in macrophages and foam cells of human atherosclerotic plaques. In the present work, we have identified plexin B2 as a putative CD100 receptor in these cells. We have detected CD100 expression in the endothelium as well as in in vitro cultured endothelial cells. Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. This effect may be mediated by CD100 expressed in both cell types, probably coupled to the receptors endothelial plexin B1 and monocytic plexin B2. These results can bring new insights about a possible biological activity of CD100 in monocyte adhesion and atherosclerosis, as well as a future candidate for targeting therapeutics.

Familial hypercholesterolemia is characterized by elevated plasma cholesterol and early coronary arterial disease onset. However, few studies investigated the association of heterozygous familial hypercholesterolemia with peripheral arterial disease.In a cross sectional study 202 heterozygous familial hypercholesterolemia patients (91% confirmed by molecular diagnosis) were compared to 524 normolipidemic controls. Peripheral arterial disease was diagnosed by ankle-brachial index values ≤0.90.Compared with controls, familial hypercholesterolemia patients were older, more often female, with higher rates of hypertension, diabetes, previous coronary disease and higher total cholesterol levels. Smoking (previous and former) was more common among controls. The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in familial hypercholesterolemia and controls (p0.001). Results persisted after matching familial hypercholesterolemia and controls by a propensity score. Regression analyses demonstrated that age (odds ratio- OR = 1.03 95% CI 1.00-1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69-11.44, p0.001) were independently associated with peripheral arterial disease. Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p = 0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p0.001) and smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral arterial disease.Peripheral arterial disease is more frequent in familial hypercholesterolemia than in normolipidemic subjects and it should routine screened in these individuals even if asymptomatic. However, its role as predictor of cardiovascular events needs to be ascertained prospectively.

Alois Alzheimer is best known for his description of the pre-senile neurodegenerative disease named after him. However, his previous interest in vascular brain diseases, underlying cognitive and behavioral changes, was very strong. Besides describing the Arteriosclerotic atrophy of the brain and the arteriosclerotic subtype of Senile dementia which he viewed as main forms of vascular brain diseases, he also identified and described a series of conditions he considered subforms. These may be divided, as suggested by the authors of the present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and apoplectic. The subforms of the three groups present characteristic neuropathological features and clinical, cognitive and behavioral manifestations. These provide the basis, together with part of the main forms, for the contemporary condition known as Vascular Cognitive Impairment.Alois Alzheimer é conhecido principalmente pela descrição de uma doença neurodegenerative pré-senil, que recebeu seu nome. Entretanto, previamente, seu interesse em doenças vasculares cerebrais, subjacentes a desordens cognitivas e comportamentais, foi muito forte. Além de descrever a Atrofia arteriosclerótica do cérebro e o subtipo arteriosclerótico da Demência senil, vistas por ele como formas principais de doenças vasculares cerebrais, ele identificou e descreveu uma série de condições que considerou como subformas. Estas podem ser divididas, como sugestão dos autores do presente artigo, em tres grupos: gliose e esclerose, atrofias subcorticais e apoplética. As subformas dos tres grupos apresentam aspectos neuropatológicas e manifestações clínicas, cognitivas e comportamentais, características. Estas forneceram a fonte, juntamente com parte das formas principais, à condição contemporânea conhecida como Comprometimento Cognitivo Vascular.

Cardiovascular disease is a cause of concern in public health worldwide, reinforcing the need for studies related to the identification of potential agents that contribute to the inflammation process and atherosclerosis. This study aimed to evaluate whether metals are associated with inflammatory and kidney damage and could contribute to the atherosclerosis process.Blood metals, inflammatory markers, homocysteine, antioxidants and renal markers were measured in 42 taxi drivers and 27 controls (non-occupationally exposed).Taxi drivers had increased Hg, As, Pb and Cd levels, however Cu and Zn levels were decreased compared to controls (p0.05). Hg, As and Pb levels were positively associated with pro-inflammatory cytokines, nitric oxide and negatively associated with glutathione peroxidase. Moreover, Hg, As and Pb presented positive associations with homocysteine, an independent risk factor for atherosclerosis. Regarding markers of kidney function, N-acetyl-beta-d-glucosaminidase levels were increased in taxi drivers and correlated to inflammation markers.Hg levels were found above the recommended limits in taxi drivers and both Hg and As levels showed associations with inflammatory process, oxidative status and homocysteine. Thus, chemical substances as Hg and As can be considered as additional contributors to the development of cardiovascular diseases.

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p