Introdução: A rigidez arterial é um fenômeno complexo caracterizado pela diminuição da complacência vascular frente aos estímulos fisiológicos e patológicos. Semelhantemente a outros fenótipos cardiovasculares, a etiologia da rigidez arterial é modulada por fatores ambientais e genéticos. Levando em consideração a moderada herdabilidade e a característica poligênica do presente fenótipo, torna-se interessante a investigação de marcadores genéticos referentes aos diferentes sistemas envolvidos no remodelamento vascular. Objetivo: Avaliar o impacto dos polimorfismos C242T da subunidade p22phox da NADPH oxidase, G1036C da TXNIP, C609T/T471C da APOE, G1355A da elastina, I/D da ECA e A855G da MMP-9 no fenótipo de rigidez arterial em uma população geral. Métodos: Participaram do estudo 1.663 indivíduos da população geral da cidade de Vitória-ES. O DNA foi extraído a partir de uma amostra de sangue venoso. Posteriormente foram realizadas as genotipagens para as variantes genéticas supracitadas. A rigidez arterial foi avaliada por meio do método da velocidade de onda de pulso (VOP). Resultados: Em relação à VOP, os polimorfismos C242T da subunidade p22phox da NADPH oxidase e G1036C da TXNIP foram signifcativamente associados. Os indivíduos portadores do genótipo TT do polimorfismo C242T da subunidade p22phox (CC+TC=9,8 m/s versus TT=10,1 m/s, p=0,02) e do alelo G do polimorfismo G1036C da TXNIP (CC=9,8 m/s versus CG+GG=10,0 m/s, p=0,03) apresentaram maiores valores da VOP. Entretanto os polimorfismos C609T/T471C da APOE (2=10,0 m/s, 3=9,8 m/s, 4=9,8 m/s, p=0,60), G1355A da elastina (AA=9,8 m/s, GA=9,9 m/s, GG=9,8 m/s, p=0,92), I/D da ECA (DD=9,8 m/s, DI=9,8 m/s, II=9,9 m/s, p=0,53) e A855G da MMP-9 (AA=9,8 m/s, GA=9,8 m/s, GG= 9,8 m/s, p=0,60) não demonstraram tal associação. Somente o genótipo TT do polimorfismo C242T da subunidade p22phox (OR=1,93, p=0,002) apresentou um risco significativamente aumentado para o fenótipo de rigidez arterial. Já os polimorfismos G1036C da TXNIP (OR=1,19, p=0,19), C609T/T471C da APOE (OR=1,14, p=0,33), G1355A da elastina (OR=0,81, p=0,28), I/D da ECA (OR=0,91, p=0,48) e A855G da MMP-9 (OR=1,01, p=0,95) não apresentaram risco. Conclusão: Os polimorfismos C242T da subunidade p22phox da NADPH oxidase e G1036C da TXNIP podem contribuir como moduladores genéticos no enrijecimento vascular / Introduction: Arterial stiffness is a complex phenomenon characterized by decreased vascular compliance during physiological and pathological stimuli. Similar to other cardiovascular phenotypes, arterial stiffness etiology is modulated by environmental and genetic factors. Considering the moderate heritability and its polygenic phenotype, genetic markers investigations related to different systems involved in vascular remodeling are interesting. Objectives: To assess the impact of the p22phox C242T, TXNIP G1036C, APOE C609T/T471C, elastin G1355A, ACE I/D and MMP-9 A855G polymorphisms on arterial stiffness phenotype in a general population. Methods: This study included 1,663 individuals of the general population from Vitória-ES. DNA was extracted from a venous blood sample and genotyping assays were performed for the genetic variants described above. Arterial stiffness was evaluated by pulse wave velocity (PWV). Results: Regarding PWV, p22phox C242T and TXNIP G1036C polymorphisms were significantly associated. Individuals carrying TT genotype of the p22phox C242T (CC + CT vs TT = 9.8 m/s = 10.1 m/s, p = 0.02) and individuals carrying G allele of the TXNIP G1036C polymorphisms (CG + CC = 9.8 m/s vs GG = 10.0 m/s, p = 0.03) had higher PWV values. However, APOE C609T/T471C (2=10.0 m/s, 3=9.8 m/s, 4=9.8 m/s, p=0.60), elastin G1355A (AA=9.8 m/s, GA=9.9 m/s, GG=9.8 m/s, p=0.92), ACE I/D (DD=9.8 m/s, DI=9.8 m/s, II=9.9 m/s, p=0.53) and MMP-9 A855G (AA=9.8 m/s, GA=9.8 m/s, GG= 9.8 m/s, p=0.60) polymorphisms did not present association. Only the TT genotype of the p22phox C242T polymorphism (OR = 1.93, p = 0.002) presented an increased risk for the arterial stiffness phenotype. Already TXNIP G1036C (OR=1.19, p=0.19), APOE C609T/T471C (OR=1.14, p=0.33), elastin G1355A (OR=0.81, p=0.28), ACE I/D (OR=0.91, p=0.48) and MMP-9 A855G (OR=1.01, p=0.95) polymorphisms did not present risk. Conclusion: The p22phox C242T and the TXNIP G1036C polymorphisms may contribute to genetic modulators in vascular stiffening

Este trabalho avaliou o efeito da dieta hiperlipídica em camundongos para o estudo da inflamação cardiovascular. Camundongos C57Bl/6 machos com 8 semanas de vida foram utilizados nos ensaios, sendo divididos nos grupos dieta controle e dieta hiperlipídica. Após 8 semanas foram avaliados: o ganho de peso, a porcentagem de tecido adiposo, pressão arterial sistólica, frequência cardíaca, perfil lipídico e glicêmico séricos. A partir de cortes histológicos de aortas e corações corados com picrossirius foram feitas análises morfométricas. Em cortes histológicos de aorta foram realizadas a análise fibras elásticas e colágenas usando a coloração de Weigert-Van Gieson. Também foram realizadas a quantificação de fibras colágenas em aortas, usando a coloração de picrossirius. Nos tecidos aórticos e cardíacos foram feitos: 1) Ensaios de atividade enzimática para ECA e MPO. 2) Ensaios de Immunoblotting para a detecção proteíca para ECA e TGF-b. Também foram feitos ensaios de imuno-histoquímica para marcação e localização de ECA e TGF-b no tecido aórtico. / This work evaluated the effect of high-fat diet in mice for the study of cardiovascular inflammation. C57BL / 6 mice at 8 weeks of age were used in the tests were divided in groups control diet and high fat diet. After 8 weeks were evaluated: weight gain, percentage of fat, systolic blood pressure, heart rate, serum lipids and glucose levels. From histological aortas and hearts stained with picrosirius morphometric analyzes. Histological sections of the aorta were performed to analyze elastic and collagen fibers using Weigert-Van Gieson staining. Also the quantification of collagen fibers in aortas using picrosirius staining. In aortic and cardiac tissues were made: 1) Enzymatic activity assays for ACE and MPO. 2) Immunoblotting assays to detect proteinous for ACE and TGF-b. Also were peformed Immunohistochemistry assays for marking and localization of ACE and TGF- b in the aortic tissue.

The tangential contact stiffness for ground Ti-6Al-4V surfaces is measured to linearly decrease with the application of tangential load. At the beginning of the application of tangential load, for ground surfaces, the ratio of the tangential contact stiffness to the normal contact stiffness is seen to be approximately half the Mindlin ratio. This is consistent with many other published experimental studies. Measurements of normal contact stiffness for ground surfaces conform to a model that posits a linear relationship between normal contact stiffness and normal load. An equivalent surface roughness parameter is defined for two surfaces in contact; and the normal contact stiffness for ground surfaces is observed to be inversely proportional to this parameter. Single asperity models were constructed to simulate the effect of different frictional laws and plasticity on the tangential displacement of an asperity contact. Further, multi-asperity modelling showed the effect of different normal load distributions on the tangential behaviour of interfaces. In addition, normal contact stiffness was modelled for a grid of asperities taking into account asperity interactions. A receding contact problem for which the required form of the distributed dislocations is bounded-bounded was solved. Then, a fundamental 2D frictional receding contact problem involving a homogeneous linear elastic infinite layer pressed by a line load onto a half-plane of the same material was analysed. This was done by the insertion of preformed distributed dislocations (or eigenstrains), which take into account the correct form of the separation of the interface at points away from the area of loading, along with corrective bounded-bounded distributions. The general method of solution was further refined and adapted to solve three other receding contact problems. The solutions demonstrated the robustness and applicability of this new procedure.

"Topographical and mechanical properties of adhesive substrates provide important biological cues that affect cell spreading, migration, growth, and differentiation. The phenomenon has led to the increased use of topographically patterned and flexible substrates in studying cultured cells. However, these studies may be complicated by various limitations. For example, the effects of ligand distribution and porosity are affected by topographical features of 3D biological constructs. Similarly, many studies of mechanical cues are compounded with cellular deformation from external forces, or limited by comparative studies of separate cells on different substrates. Furthermore, understanding cell responses to mechanical input is dependent upon reliable measurements of mechanical properties. This work addresses each of these issues. To determine how substrate topography and focal adhesion kinase (FAK) affect cell shape and movement, I studied FAK-null (FAK -/-) and wild type mouse 3T3 fibroblasts on chemically identical polystyrene substrates with either flat surfaces or micron-sized pillars, I found that, compared to cells on flat surfaces, those on pillar substrates showed a more branched shape, an increased linear speed, and a decreased directional stability, which were dependent on both myosin-II and FAK. To study the dynamic responses to changes in substrate stiffness without other confounding effects, I developed a UV-modulatable substrate that softens upon UV irradiation. As atomic force microscopy (AFM) proved inadequate to detect microscale changes in stiffness, I first developed and validated a microsphere indentation method that is compatible with fluorescence microscopy. The results obtained with this method were comparable to those obtained with AFM. The UV-modulatable substrates softened by ~20-30% with an intensity of irradiation that has no detectable effect on 3T3 cells on control surfaces. Cells responded to global softening of the substrate with an initial retraction followed by a gradual reduction in spread area. Precise spatial control of softening is also possible - while there was little response to posterior softening, anterior softening elicited a pronounced retraction and either a reversal of cell polarity or a significant decrease in spread area if the cells move into the softened region. In conclusion, these techniques provide advances in gaining mechanistic insight into cellular responses to topographical and mechanical cues. Additionally, there are various other potential applications of the novel UV-softening substrate, particularly in regenerative medicine and tissue engineering. "

Cells respond to their mechanical environment by changing shape and size, migrating, or even differentiating to a more specialized cell type. A better understanding of the response of cells to surrounding cues will allow for more targeted and effected designs for biomedical applications, such as disease treatment or cellular therapy. The spreading behavior of both human mesenchymal stem cells (hMSCs) and 3T3 fibroblasts is a function of substrate stiffness, and can be quantified to describe the most visible response to how a cell senses stiffness. The stiffness of the substrate material can be modulated by altering the substrate thickness, and this has been done with the commonly-used linearly elastic gel, polyacrylamide (PA). Though easy to produce and tune, PA gel does not exhibit strain-stiffening behavior, and thus is not as representative of biological tissue as fibrin or collagen gel. Fibroblasts on soft fibrin gel show spreading similar to much stiffer linear gels, indicating a difference in cell stiffness sensing on these two materials. We hypothesize cells can sense further into fibrin and collagen gels than linear materials due to the strain-stiffening material property. The goal of this work is to compare the material response of linear (PA) and strain-stiffening (fibrin, collagen gel) substrates through modulation of effective stiffness of the materials. The two-step approach is to first develop a finite element model to numerically simulate a cell contracting on substrates of different thicknesses, and then to validate the numerical model by quantifying fibroblast spreading on sloped fibrin and collagen gels. The finite element model shows that the effective stiffness of both linear and nonlinear materials sharply increases once the thickness is reduced below 10µm. Due to the strain-stiffening behavior, the nonlinear material experiences a more drastic increase in effective stiffness at these low thicknesses. Experimentally, the gradual response of cell area of HLF and 3T3 fibroblasts on fibrin and collagen gels is significantly different (p<0.05) from these cell types on PA gel. This gradual increase in area as substrate thickness decreases was not predicted by the finite element model. Therefore, cell spreading response to stiffness is not explained by just the nonlinearity of the material.

Cardiovascular disease is the leading cause of death in the developed world. The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Passive heat stress results in elevations in core temperature (inducing heat shock protein expression) and changes in cardiovascular hemodynamics, such as increased cardiac output and shear stress, that are similar to exercise. Thus, repeated passive heat stress (“heat therapy”) may provide an alternative means of improving cardiovascular health, particularly for patients with limited exercise tolerance and/or capabilities. Therefore, the goal of this dissertation was to perform integrative studies to determine the effects of heat therapy on vascular function and the associated cellular pathways in young, sedentary humans. Twenty subjects were assigned to participate in 8 weeks (4-5x/week) of heat therapy (N=10; immersion in a 40.5°C bath sufficient to maintain rectal temperature ≥38.5°C for 60 min/session) or thermoneutral water immersion (N=10; sham). As discussed in Chapter V, we found that heat therapy improved numerous well-established biomarkers of conduit vessel/macrovascular function, including flow-mediated dilation (a measure of endothelial function), arterial stiffness, intima media thickness, and blood pressure. Heat therapy also improved microvascular function, as discussed in Chapter VI, measured as improved cutaneous thermal hyperemia and nitric oxide-dependent dilation (the difference between microdialysis sites receiving Lactated Ringer’s [control] and nitric oxide synthase inhibition). No changes were observed in any variables in sham subjects. In Chapter VII, we showed that both direct cellular heating and serum collected from human subjects following heat therapy improved nitric oxide bioavailability and angiogenesis in cultured endothelial cells, providing potential mechanisms by which heat therapy improves vascular function in vivo. Therefore, the studies described herein provide comprehensive evidence that passive heat therapy improves vascular health and insight into the mechanisms involved. Our data presented in Chapters IV-VII, combined with pilot data we conducted in spinal cord injured individuals (Chapter VIII), strongly indicate that passive heat therapy could be used as a simple and effective tool to improve cardiovascular health in a variety of patient populations. This dissertation includes published and unpublished co-authored material.

A engenharia geotécnica frequentemente tem limitações de caráter econômico e ambiental. É por isso que a técnica de melhoramento das propriedades do solo pode se tornar uma alternativa de solução em diversos casos, como na construção de bases de pavimentos, camada de suporte em fundações superficiais, revestimento de canais e na proteção de taludes em barragens. Este trabalho faz parte de uma dissertação de mestrado que tem por objetivo avaliar a influência do teor de umidade de compactação, peso específico aparente seco e teor de agente cimentante na durabilidade, rigidez e resistência de um solo fino artificialmente cimentado. Para isso foram realizados ensaios de compressão simples após ciclos de molhagem e secagem, ensaios de perda de massa, rigidez inicial e ensaios de compressão triaxial. Os resultados mostraram que quanto maior o teor de cimento, o peso específico aparente seco e o teor de umidade para os teores estudados (17%, 20%, e 23%), maior é a resistência e menor é a queda da rigidez inicial após ciclos de molhagem e secagem, assim também menor é a perda de massa, mostrando um melhor desempenho quanto à durabilidade. Verificou-se que a metodologia apresentada por Consoli (2014) é válida para a previsão de parâmetros de resistência ao cisalhamento de solos com diferentes teores de umidade. / Geotechnical engineering often has limitations of economic and environmental natures, which is why the ground improvement technique can become an alternative solution in many cases, as in pavement base layers, support layers under shallow foundations, canal coating and in slope protection of earth dams. This work is part of a M.Sc. dissertation, which aims to assess the influence of the moisture content, porosity and cement content on durability, initial stiffness and strength of an artificially cemented fine-grained soil. A number of unconfined compression tests were carried out after wetting and drying cycles, together with weight loss and initial shear stiffness tests. Triaxial compression tests were also done. The results show that as higher the amount of cement, porosity and moisture content for the studied concentrations (17%, 20% and 23%), the greater is the resistance and lower is the drop of initial stiffness after wetting and drying cycles, as well as smaller the weight loss, showing a better performance in terms of durability. It was verified that, the methodology presented by Consoli (2014) is valid for predicting soil shear strength parameters with different moisture contents.

O exercício excêntrico tem sido utilizado na prevenção/reabilitação de lesões e em programas de treinamento de força para melhorar o condicionamento físico de indivíduos saudáveis. O entendimento das adaptações causadas pelo treinamento excêntrico nos músculos flexores plantares se justifica: 1) pela importância desta musculatura na manutenção de posturas e no ciclo da marcha; 2) pela alta incidência de lesões do tendão de Aquiles; e 3) pelo uso sistemático deste tipo de treinamento em programas de prevenção e reabilitação do tríceps sural. Assim, a presente tese de doutorado busca verificar os efeitos do treinamento excêntrico nas propriedades neuromecânicas e morfológicas dos músculos flexores plantares. No capítulo I foram compiladas informações acerca das adaptações neuromusculares dos flexores plantares e do tendão de Aquiles de indivíduos saudáveis submetidos à programas de treinamento excêntrico. Os estudos encontrados indicam que o treinamento excêntrico pode aumentar a produção de força e ativação muscular, especialmente em testes excêntricos. No entanto, resultados conflitantes e lacunas identificadas na literatura motivaram a realização de dois estudos originais. Os objetivos dos estudos originais foram: 1) determinar a temporalidade das adaptações na ativação e massa muscular de flexores plantares, bem como sua contribuição para os ganhos de força em contrações excêntricas, isométricas e concêntricas ao longo do programa de treinamento (Capítulo II); e 2) avaliar os efeitos de 12 semanas de treinamento excêntrico nas propriedades morfológicas, mecânicas e materiais do tendão de Aquiles de indivíduos saudáveis (Capítulo III). Vinte participantes do sexo masculino realizaram um programa de treinamento excêntrico isocinético (duas vezes por semana, 3-5 séries de 10 repetições máximas). As avaliações das propriedades neuromecânicas e morfológicas dos flexores plantares foram realizadas a cada quatro semanas. Ao final de 12 semanas, o programa de treinamento excêntrico aumentou a produção de torque máximo excêntrico, isométrico e concêntrico; aumentou a atividade eletromiográfica máxima excêntrica e isométrica; e aumentou a espessura muscular. Além disso, os ângulos do pico de torque excêntrico e concêntrico foram deslocados para posições em que os músculos estavam mais alongados. O torque máximo e a espessura muscular aumentaram progressivamente até a oitava semana de treinamento. A ativação neural durante contrações excêntricas e isométricas aumentou após quatro semanas de treino e permaneceu constante até o final do treinamento, enquanto que a ativação neural durante contrações concêntricas permaneceu inalterada durante todo o período de treinamento. Além disso, houve aumento da área de secção transversa, da rigidez e do módulo de Young do tendão de Aquiles. Os incrementos na rigidez e no módulo de Young foram observados após quatro semanas de treinamento, enquanto que o aumento significativo da área de secção transversa tendínea ocorreu após oito semanas de treinamento. Quando tomados em conjunto, estes resultados nos possibilitam entender de que forma as adaptações neuromecânicas e morfológicas dos flexores plantares ocorrem. O aumento da força isométrica e excêntrica nas primeiras quatro semanas de treinamento parece ocorrer devido a adaptações neurais, musculares e tendíneas. No entanto, após maiores períodos de treinamento (i.e. acima de quatro semanas), o aumento da força ocorre devido a incrementos na massa muscular e na rigidez tendínea. Além disso, a ausência de adaptações neurais evidencia que os ganhos de força concêntrica podem estar relacionados apenas com adaptações musculares e tendíneas. / Eccentric exercises are commonly used in prevention, rehabilitation and conditioning training programs. Understanding the adaptations caused by eccentric training on the plantar flexor muscles is justified by: 1) the importance of these muscles in maintaining posture and during gait cycle; 2) the high incidence of Achilles tendon injuries; and 3) the systematic use of this type of training in triceps surae prevention and rehabilitation programs. Thus, the present PhD thesis aims to verify the effects of eccentric training in neuromechanical and morphological properties of the plantar flexor muscles. Chapter I compiled information about the neuromuscular adaptations of the plantar flexors and Achilles tendon of healthy subjects undergoing eccentric training programs. The studies found indicate that eccentric training can increase the production of muscle strength and muscle activation, especially in eccentric tests. The studies found indicate that eccentric training can increase muscle strength and muscle activation, especially in eccentric tests. The purposes of the original studies were: 1) to determine the adaptations time course in plantar flexors activation and muscle mass, as well as their contribution to the strength gains in eccentric, isometric and concentric contractions during the training program (Chapter II); and 2) to evaluate the effects of 12 weeks of eccentric training on Achilles tendon morphological, mechanical and material properties in healthy subjects (Chapter III). Twenty male subjects performed an eccentric isokinetic training program (twice a week, 3-5 sets of 10 maximal repetitions). Plantar flexor neuromechanical and morphological evaluations were performed every 4 weeks. The 12-week training program led to increases in maximum eccentric, isometric and concentric torques; maximum eccentric and isometric electromyographic activity; and muscle thickness. The angles of peak torque in eccentric and concentric tests were shifted towards longer muscle lengths. Maximum torque and muscle thickness increased progressively until the 8th training week. Eccentric and isometric activation increased up to the 4th training week and remained constant until the 12th training week, while no change was found in concentric activation. In addition, Achilles tendon cross-sectional area, stiffness and Young's modulus were increased. The increases in stiffness and Young's modulus were observed after four weeks of training, while the significant increase in tendon cross-sectional area occurred after eight weeks of training. Taken together, these results allow us to understand how the neuromechanical and morphologic adaptations occur in the plantar flexors muscles subjected to a 12-week eccentric training program. The increase in isometric and eccentric strength in the first four weeks of training seems to be related to neural, morphological and tendinous adaptations. However, after longer training periods (i.e. up to four weeks), the strength increase is due to increases in muscle mass and tendon stiffness. Moreover, the absence of evidence in terms of neural adaptations during concentric contractions suggest that the concentric strength gains seem to be related only with muscle and tendon adaptations.

A greater understanding of precessional dynamics in magnetic systems is central to several emerging technologies. This thesis presents the design, construction and development of a Vector Network Analyser based Ferromagnetic Resonance measurement instrument (VNA-FMR), and its application in characterising dynamic material properties in hybrid anisotropy [CoPd]8-NiFe films, produced by remote plasma sputtering. Potential applications for hybrid films include Spin Torque Oscillators (STOs) or Vortex Oscillators (VO) for use as microwave emitters in, for example in Microwave Assisted Magnetic Recording (MAMR). The VNA-FMR system was first used to measure thin films of NiFe (permalloy) which allowed its capabilities to be quantified and compared to systems reported in the literature. The instrument demonstrated the capability of measuring permalloy films down to a thickness of 3 nm and was used to measure resonance and damping behaviour which agreed well with theory. The results obtained forMs were in agreement with measurement using Vibrating Sample Magnetometry. The effect of interlayer exchange on FMR was explored in hybrid films using a sample series with varying Pd spacer layer thickness, t, [Co/Pd]-Pd(t)-NiFe. As Pd spacer thickness increased, a transition was observed from near complete coupling with a single resonance mode to separate acoustic and optical branches of resonance. As spacing was further increased, the branches converged towards the resonances of the individual component layers of the hybrid films. The results suggest exchange coupling has a range of less than 2 nm, and is completely extinguished at 5 nm, in agreement with previous measurements. However, a change in damping behaviour was observed between 10 and 20 nm spacer thickness, independent of field orientation.

La polyarthrite rhumatoïde (PR) est une maladie inflammatoire, auto-immune, chronique et systémique avec la présence d’arthrites et synovites périphériques. Une autre conséquence sévère de la maladie et de ses traitements est la présence d’une rigidité artérielle élevée précoce, par conséquent une haute incidence de problèmes cardiovasculaires pour les sujets atteints. La pratique d'exercices physiques (EP) est reconnue comme une des thérapies non-pharmacologiques les plus efficaces pour lutter contre le risque cardiovasculaire. Cependant la population PR présente un bas niveau de pratique d’activité physique et les programmes d’EP sont rarement proposés dans la prise en charge thérapeutique de ces patients. Pour dépasser cette problématique l’association de la cryothérapie à un programme d’EP adapté semble être une stratégie intéressante. L’objectif de ce travail était de concevoir et de tester un programme d’EP associé à de la cryothérapie adapté aux patients PR afin de lutter contre le risque cardiovasculaire.A partir d’une revue systématique, nous avons montré le caractère lacunaire de la littérature en termes de programme d’EP associé à de la cryothérapie pour des patients PR, le manque de consensus sur les méthodes utilisées aussi bien pour le type d’EP à proposer que pour les méthodes de cryothérapie et les températures employées. Face à cette situation, nous avons proposé plusieurs études préliminaires afin de déterminer les modalités d’exercice et de cryothérapie les plus appropriées pour définir un programme simple, efficace et adapté aux patients PR. Ces travaux ont été réalisés d’une part avec des sujets sains et d’autre part avec des patients PR. Nous avons également entrepris de mieux définir les conditions d’utilisation de la vitesse de propagation de l’onde de pression pour traduire la rigidité artérielle, afin d’utiliser cette dernière comme un marqueur des effets de nos propositions de programme d’EP sur le risque cardiovasculaire. Enfin nous avons tenté d’évaluer quels pouvaient être les freins à la pratique d’EP pour ces patients afin de pouvoir les prendre en compte et les contourner dans la mise en place de nos propositions. Les principaux résultats de nos travaux nous ont permis de définir les caractéristiques d’un programme d’EP associé à de la cryothérapie pour des patients PR afin d’agir sur leur rigidité artérielle.Ce programme, intitulé Prexcrim, a été mise en œuvre avec un groupe de patients atteints de PR. Les premiers résultats que nous avons obtenus confirment la faisabilité de nos propositions et la bonne tolérance des patients. Aucune sortie de l’étude ou effet secondaire a été observé. A ce stade des inclusions et de l’analyse des résultats, il semble que le programme d’EP proposé permette de modifier la rigidité artérielle en particulier des patients qui présentaient une rigidité artérielle élevée au départ. Il n’a pas été observé d’aggravation de la maladie ou du syndrome inflammatoire ce qui semble renforcer l’intérêt de la méthode de cryothérapie proposée. Les inclusions qui se poursuivent permettront sans doute d’affiner ces premières interprétations.En conclusion, notre travail a permis de combler une partie des lacunes constatées dans la littérature en termes de lutte contre le risque cardiovasculaires accru constaté chez les patients PR. Notre approche a permis la réalisation d’un programme simple et facile d’EP associé à de la cryothérapie, dont les premiers résultats répondent aux attentes fixées. Les premières analyses que nous avons réalisées montrent que les principes d’individualisation et de progressivité seront certainement à améliorer pour optimiser les effets du programme. / Rheumatoid arthritis (RA) is an inflammatory, autoimmune, chronic and systemic disease with the presence of arthritis and peripheral synovitis. Another severe consequence of the disease and its treatments is the presence of early high arterial stiffness, hence a high incidence of cardiovascular problems for the subjects with RA. The practice of physical exercises (PE) is recognized as one of the most effective non-pharmacological therapies against the cardiovascular risk. However, the RA population has a low level of physical activity and PE programs are rarely offered in the therapeutic management of these patients. To overcome this problem, the association of cryotherapy to an appropriate PE program seems to be an interesting strategy. The objective of this work was to design and test a PE program associated with cryotherapy adapted to patients with RA in order to fight against the cardiovascular risk.From a systematic review, we have shown the lack of the literature in terms of PE program associated with cryotherapy for patients with RA, the lack of consensus on the methods used for both the type of PE to be proposed and the cryotherapy methods and temperatures employed. Consequently, we have proposed several preliminary studies to determine the most appropriate exercise and cryotherapy modalities for defining a simple, effective and suitable program. These works were carried out firstly in healthy subjects and after in patients with RA. We have also undertaken to better define the used conditions of the pulse wave velocity to interpret arterial stiffness and use it as a marker of effects of our PE program on cardiovascular risk. Finally, we tried to evaluate what could be the obstacles to the practice of PE for these patients, to consider and overcome them in the implementation of our proposals. The main results of our works allowed us to define the characteristics of a PE program associated with cryotherapy for patients with RA to act on their arterial stiffness.This program, entitled Prexcrim, was implemented with a group of patients with RA. The first results confirmed the feasibility of our proposals and the good tolerance of patients. No study output or side effect was observed in the patients. At this stage of inclusion and analysis of the results, it appears that the proposed PE program allows for changes in arterial stiffness, particularly for patients with high arterial stiffness. It was not observed exacerbation of the disease or inflammatory syndrome, which seems to reinforce the interest of the proposed cryotherapy method. The inclusions that continue will undoubtedly refine these first interpretations.In conclusion, our work proposes some responses about the lack in terms of the fight against the increased cardiovascular risk observed in patients with RA. Our approach allowed the realization of a simple and easy PE program associated with cryotherapy. The first results meet our expectations. The first analyzes shown that the principles of individualization and progressivity need to be improved to optimize the effects of the program.