L'hypertrophie ventriculaire gauche (HVG) est un remodelage prédicteur du développement d'une insuffisance cardiaque et de la mortalité cardiovasculaire. L'hypertension artérielle est une cause majeure de l'HVG, puisque 30% des patients hypertendus développent une HVG. Un dépistage biologique précoce de l'HVG post hypertensive permettrait d'optimiser la prise en charge des patients et d'empêcher que l'HVG évolue vers l'insuffisance cardiaque. L'utilisation de biomarqueurs est un outil rapide, efficace et peu couteux pour le diagnostic de nombreuses pathologies. Dans la pratique clinique il n'existe pas de biomarqueurs pour identifier les patients hypertendus avec HVG de ceux sans ce remodelage. Le premier objectif de notre étude a été d'identifier des biomarqueurs plasmatiques de l'HVG post hypertensive. Une analyse métabolomique obtenue par spectroscopie de résonance magnétique nucléaire du proton (H1) a été effectuée sur les échantillons de plasma de 48 patients hypertendus avec HVG, 48 hypertendus sans HVG et 24 témoins. A l'aide d'outils bio-informatiques et d'analyses statistiques adaptées, nous avons mis en évidence la présence d'un ratio des groupements chimiques méthylène/ méthyle (-CH2-/-CH3) des chaines aliphatiques des lipides plasmatiques augmenté chez les patients hypertendus avec HVG (p<0.001). Ce ratio détecte la présence d'une HVG chez les patients hypertendus avec une sensitivité de 52.08% et une spécificité de 85.42%. Nous proposons que le ratio -CH2-/-CH3 des chaines aliphatiques lipidiques présent dans plasma représente un biomarqueur diagnostique de l'HVG dans l'hypertension artérielle. L'incidence de l'HVG est aussi augmentée chez les patients qui souffrent du syndrome métabolique (MetS). Le MetS est défini par la présence d'une obésité abdominale plus deux facteurs parmi la dyslipidémie, l'insulino-résistance et l'hypertension artérielle. Ces facteurs synergisent et sont les responsables de l'instauration d'une HVG et d'une progression vers l'insuffisance cardiaque. Des données publiées montrent que les patients MetS ont un taux réduit de l'insulin-like growth factor binding protein 2 (IGFBP2). L'IGFBP2 a un rôle potentiel dans le diabète et dans le métabolisme, mais il n'existe pas d'étude sur son rôle dans les pathologies cardiaques causées par une dérégulation métabolique. Le premier objectif de notre étude sur l'IGFBP2 a été de mesurer le taux plasmatique d'IGFBP2 et le taux d'expression cardiaque de l'ARN messager d'IGFBP2 dans une cohorte de patients avec et sans MetS. Nous avons montré que le taux plasmatique ainsi que le taux d'ARN messager cardiaque d'IGFBP2 sont diminués chez les patients avec le Mets comparé à des témoins. Puis, nous avons mesuré le tôt cardiaque d'ARN messager de l'IGFBP2 dans un model murin de MetS. Pour générer ce modèle, nous avons nourri des souris C57BL/6J avec du régime gras à 60% pendant 15 semaines. Le taux d'expression cardiaque de l'ARN messager de l'IGFBP2 est réduit chez les souris avec Mets, en accord avec les résultats obtenu chez l'homme. Enfin, nous avons testé si la thérapie génique utilisant un virus adeno-associé qui exprime l'IGFBP2 humaine (AAV9-hIGFBP2) pouvait restaurer un niveau normal d'IGFBP2 et interférer avec l'HVG causé par le MetS chez ces souris. Nos résultats montrent que l'injection de l'AAV9-hIGFBP2 rétabli durablement le niveau cardiaque d'IGFBP2 chez la souris avec MetS et qu'IGFBP2 prévient l'épaississement des parois du ventricule gauche, l'hypertrophie et la dysfonction cardiaque. Nos résultats suggèrent qu'IGFBP2 est une nouvelle cible thérapeutique potentielle de l'HVG. / Left ventricular hypertrophy (LVH) is a strong predictor of future heart failure and cardiovascular mortality. Arterial hypertension is considered as the main causative agent for LVH as 30% of hypertensive patients develop LVH. These patients have an increased risk for cardiovascular complications and heart failure. Early diagnosis of LVH and prompt treatment are crucial to reduce LVH and stop its progression towards heart failure. Biomarkers could represent a rapid, effective and low-cost tool to discriminate hypertensive patients with LVH from those with normal LV size. Therefore, we aimed to identify plasma metabolomics biomarkers by 1H NMR to provide novel diagnostic tools for rapid detection of LVH in populations of hypertensive individuals. We realized a cross-sectional study including 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the 1H NMR spectral data. From the 1H NMR analysis, we found that the methylene/methyl (-CH2-/-CH3) ratio of aliphatic chain from plasma lipids was significantly increased (p<0.001) in hypertensive patients with LVH compared to hypertensive patients without LVH and to control. Receiver operating characteristic curve showed that a cutoff value of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC=0.703, p-value<0.001). We propose the -CH2/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of LVH in arterial hypertension. LVH incidence is also increased in patients with metabolic syndrome (MetS). MetS is defined by central obesity plus any two medical conditions such as dyslipidemia, insulin resistance, and hypertension. These factors synergize to cause LV dysfunction and HF. Published data have shown that MetS patients have low plasma insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 was shown to play a role in diabetes and metabolism, but studies investigating its role in cardiac diseases are lacking. We first aimed to investigate plasma IGFBP2 levels and cardiac IGFBP2 mRNA levels in MetS patients. Both plasma levels and heart expression levels of IGFBP2 were decreased in patients with MetS compared to control patients. Further, in a C57BL/6J mouse model of 60% high fat diet-induced MetS, we measured cardiac mRNA IGFBP2 levels. According to the observed data in human, mice with MetS showed a decreased cardiac IGFBP2 mRNA level. Finally, we investigated whether a gene therapy strategy using adeno-associated virus 9 carrying human IGFBP2 coding sequence (AAV9-hIGFBP2) could prevent from MetS associated left ventricular hypertrophy. Our data showed that AAV9-hIGFBP2 injection restored durably cardiac IGFBP2 levels in mouse heart and prevented from left ventricle wall thickening, hypertrophy and dysfunction. These clinical and animal data suggest that IGFBP2 is a potential new cardiac therapeutic target in MetS.

Alterações cardiovasculares e hiperlipidemias são comuns em cães obesos. As apolipoproteínas (Apos) constituem um componente importante do perfil lipídico e, pelo menos em humanos, auxiliam na determinação do risco de aterosclerose, doenças vasculares e cardíacas. Sendo assim, o objetivo deste estudo foi relacionar a ocorrência de alterações cardiovasculares com fatores associados à aterosclerose, verificando também a influência da perda de peso sobre tais fatores e os parâmetros cardíacos e pressóricos. Vinte cadelas castradas, sendo 9 com ECC 4-5 (grupo controle) e 11 com ECC 8-9 (grupo obesidade) participaram desta pesquisa. Em relação ao grupo controle, o grupo obesidade apresentou o aumento da: massa gorda (em Kg e %), contagem de leucócitos, pressão arterial (PA) sistólica, concentração de triglicérides e VLDL, além da maior observação de cistites e de sinais de hipertrofia ventricular. Estes parâmetros se aproximaram da situação controle, após o emagrecimento, exceto pela ocorrência de cistites. Comparando-se os valores médios, os grupos controle e obesidade não diferiram nas avaliações eletrocardiográfica e ecocardiográfica e, tão pouco, nas concentrações de Apo A-I e B. Os resultados indicam que a redução da gordura corporal traz benefícios, devido à diminuição da concentração de colesterol (total, LDL e VLDL) e triglicérides, além da melhora nos parâmetros da avaliação cardiovascular. Além disso, a determinação das Apo A-I e Apo B podem auxiliar na avaliação do perfil lipídico, mas não apresentaram relação com as alterações cardiovasculares observadas nas cadelas obesas. / Cardiovascular alterations and hyperlipidemia are common in obese dogs. In humans, apolipoproteins (Apos) are part of lipid profile and are used to determine the atherosclerosis, vascular and cardiac diseases risks. Therefore, the objective of this study was to relate the cardiovascular changes with atherosclerotic factors, also verifying the weight loss influence on such factors and cardiac and pressure parameters. Twenty neutered dogs female, 9 with ECC 4-5 (control group) and 11 with ECC 8-9 (obesity group) participated of this study. In relation to control group, the obesity group presented the increase of: fat mass (in kg and %), leukocyte counts, systolic blood pressure (BP), triglyceride and VLDL concentrations, as well as the higher number of females with cystitis and ventricular hypertrophy signs. These parameters returned the control situation after weight loss, except the cases of cystitis. Comparing the mean values, the control and obesity groups did not differ in the electrocardiographic and echocardiographic evaluations and in Apo A-I and B concentrations. The results indicate that the reduction of body fat has benefits, due to cholesterol (total, LDL and VLDL) and triglycerides decrease and improvement of cardiovascular evaluation. In addition, Apo A-I and Apo B determination may assist in lipid profile assessing, but were not related to cardiovascular changes observed in obese female dogs.

Frente ao treinamento físico, o organismo está sujeito a alterações anatomofisiológicas em vários sistemas, especialmente o sistema músculo-esquelético. Pretendeu-se, descrever alterações no trofismo muscular do sóleo e das propriedades mecânicas das tíbias de ratos submetidos a treinamento físico em esteira rolante (TFER), bem como analisar estas relações com o tempo de treinamento. Utilizou-se de 40 ratos (20 treinados e 20 controles) da linhagem Wistar, treinados 60 min/dia, 5 dias por semana, durante 3, 6, 9 e 12 semanas, totalizando 8 grupos de 5 ratos cada. Os grupos controles foram submetidos aos mesmos procedimentos experimentais, com exceção da aplicação do treinamento físico. Após o sacrifício, o tecido muscular foi retirado unilateralmente, congelado e, posteriormente foram corados pela técnica de Hematoxilina e Eosina, para análise das áreas das fibras musculares. Para análise das propriedades mecânicas, 80 tíbias (direita e esquerda) foram medidas e pesadas e, posteriormente, realizados os ensaios de flexão em três pontos para obtenção das propriedades de carga máxima e rigidez. Após aplicação do teste ANOVA, quando comparados os grupos treinados (T) e não treinados (NT) encontramos que o TFER altera, significantemente (p < 0,05), e de maneira crescente com o tempo de treinamento, as características de hipertrofia muscular e as propriedades mecânicas de flexão das tíbias dos ratos treinados / Facing the physical training, the agency is subject of alterations anatomophysiological in several systems, specially the muscle and bone system. It is intended, to describe alterations of muscle trophy of the soleus and of the mechanical properties of the rat tibia submitted to physical training in rolling mat (PTRM), as well as like analyze these relations with the time of training. It was used 40 rats (20 training and 20 controls) of the lineage Wistar, coached 60 min/day, 5 days/week, during 3, 6, 9 and 12 weeks, totalling up to 8 groups of 5 each rats. The groups controls were submitted to the same experimental procedures, with exception of the application of the physical training. After the sacrifice, the muscle weave was withdrawn unilaterally, frozen and, subsequently were paintting by the technical one of Hematoxilina and Eosina, for analysis of the areas of the muscle fibers. For the analysis of the mechanical properties, 80 tibia (right and left) were measured and weighted and, subsequently, carried out the attempt of inflection in three points bending to obtain of the properties of maximum load and module of Young. After application of the test ANOVA, when compared the groups training (T) and controls (C) we found that the PTRM alters, significantly (p < 0,05), and going up with the time of training, the characteristics of muscle hypertrophy and the mechanical properties of inflection of the tibia of the rats training

Tem sido sugerido que combinar o treinamento de força (TF) com o treinamento com vibração (TV) pode ser mais vantajoso do que realizar o TF isolado. OBJETIVOS: Foi objetivo deste estudo avaliar os efeitos da combinação do TF com o TV (TF+V) sobre o desenvolvimento de hipertrofia e os desempenhos da força máxima dinâmica de membros inferiores (FMD) e do salto vertical (SV). Investigou-se também se os benefícios proporcionados pelo treinamento são acompanhados por alterações agudas e crônicas na excitabilidade das vias reflexas. METÓDOS: Foram realizados dois experimentos. No primeiro, foram avaliados os efeitos de uma sessão de treinamento sobre o desempenho do SV e excitabilidade das vias reflexas. Doze sujeitos do sexo masculino foram submetidos a quatro condições experimentais. Na condição TF, realizaram cinco séries de 10 repetições do exercício agachamento, com 90% da massa corporal. Nas condições TF+V30 e TF+V50, o TF foi realizado sobre a plataforma vibratória nas freqüências de 30 Hz (2-4 mm) e 50 Hz (4-6 mm), respectivamente. Na condição controle (C), os sujeitos permaneceram em repouso. Antes e depois de todas as condições experimentais, foram mensurados o desempenho do SV, e os reflexos de Hoffmann (H com amplitude de 20% da onda M máxima, H20%) e tendíneo máximo (Tmáx), no músculo sóleo. No segundo experimento, 29 sujeitos do sexo masculino foram divididos aleatoriamente nos grupos TF, TF+V30 e TF+V50. Os três grupos realizaram entre 3-5 séries de 6-12 RM do exercício agachamento, duas vezes por semana, durante dez semanas. Os grupos TF+V30 e TF+V50 fizeram o agachamento sobre a plataforma vibratória nas freqüências de 30 Hz (amplitude de 2-4 mm) e 50 Hz (amplitude de 4-6 mm), respectivamente. Antes e depois do período de treinamento, foram avaliados a área de secção transversa do quadríceps femoral (ASTQ), os desempenhos da FMD e do SV, os reflexos H e T máximos (Hmáx e Tmáx) e a onda M máxima (Mmáx), no músculo sóleo. RESULTADOS: No primeiro experimento, não foram verificadas alterações significantes na amplitude de H20% em nenhuma das condições (p>0,05). Houve diminuições significantes na amplitude das ondas Tmáx, nas condições TF (-7,4%) e TF+V50 (-11,1%), no primeiro minuto, em comparação ao período antes da intervenção (p<0,001). Foram verificadas diminuições significantes na altura do SV após a realização de todas as condições (C= -11,8%, TF= -6,6%, TF+V30= -7,7% e TF+V50= -7,4%) (p<0, 001). Não houve diferenças significantes entre grupos em nenhuma das variáveis (p>0,05). No segundo experimento, após as dez semanas de treinamento, foram verificados aumentos significantes na ASTQ (TF= 9,8%, TF+V30= 11,7%, TF+V50= 12,9%); na FMD (TF= 16,9%, TF+V30= 15,2%, TF+V50= 16,6%) e na altura do SV (TF= 6,0%, TF+V30= 7,2%, TF+V50= 6,0%) para os três grupos (p<0,05). Não houve diferença significante entre grupos em nenhuma das três variáveis. O período de treinamento não causou alterações significantes nas razões Hmáx/Mmáx (TF = +28%, TF+V30 = -16,3%, TF+V50 = -14%) e Tmáx/Mmáx (TF = -30,3%, TF+V30 = -38,2%, TF+V50 = -28,1%) (p>0,05). Contudo, foi verificado efeito principal de tempo significante para a razão Tmáx/Mmáx (-48,9%) (p<0,05). CONCLUSÕES: A realização de uma sessão de treinamento de força causa uma breve redução da atividade dos fusos musculares. Essa redução não é ampliada quando o TF é combinado com vibração. Realizar um período de TF sobre a plataforma de vibração não proporciona qualquer aumento adicional na ASTQ ou nos desempenhos da FMD e do SV, em relação ao que pode ser conseguido através do TF / It has been suggested that the combination of strength and vibration training may be advantageous when compared with strength training alone. OBJECTIVES: The aim of this study was to assess the effects of combined strength training and vibration (ST+V) on lower limb hypertrophy and on maximal dynamic strength (MDS) and vertical jump (VJ) performances. In addition, we investigate if the training-induced adaptations were in agreement to acute and chronic changes on spinal reflex excitability. METHODS: Two experiments were performed. In the first experiment, the effects of a single training session on VJ performance and spinal reflexes excitability were assessed. Twelve young male undertook four experimental conditions. On ST condition, subjects performed five sets with 10 repetitions on squat exercise with load of 90% body mass. On both ST+V30 and ST+V50 conditions, subjects performed the ST on a vibration platform at 30 Hz (2-4 mm) and 50 Hz (4-6 mm), respectively. In C condition, subjects were only assessed. Vertical jumping performance and Hoffman (at 20% of maximal M wave, H20%) and maximal tendon soleus reflexes (Tmáx) were measured before and after all experimental conditions. In the second experiment, twenty nine young male were randomized into three groups. All groups performed 3-5 sets with 6-12 RM on squat exercise, twice a week, for ten weeks. The ST+V30 and ST+V50 groups performed the squat exercise on the vibration platform at 30 Hz (2-4 mm) and 50 Hz (4-6 mm), respectively. Quadriceps cross sectional area (QCSA), MDS and VJ performances, maximal soleus H- and T- reflexes and maximal M wave (Mmáx) were assessed before and after the 10-week training period. RESULTS: in the first experiment, no significant changes were found in H20% amplitude in any experimental condition (p>0,05). Significant decrease on Tmáx amplitude was found after ST+V30 (-7.4%) and ST+V50 (-11.1%) conditions, after the first minute, compared to before intervention assessment. VJ decreased in all experimental conditions (C= -11.8%, ST= -6.6%, ST+V30= -7.7% and ST+V50= -7.4%) (p<0.001). There were no significant changes between groups in any variable measured (p>0.05). In the second experiment, significant increases were found in QCSA (ST= 9.8%, ST+V30= 11.7%, ST+V50= 12.9%); MDS (ST= 16.9%, ST+V30= 15.2%, ST+V50= 16.6%) and VJ height (ST= 6.0%, ST+V30= 7.2%, ST+V50= 6.0%) in all groups (p<0.05). There were no significant changes between groups in any variable measured (p>0.05). The training period did not induce significant changes in Hmáx/ Mmáx (ST = +28%, ST+V30 = -16,3%, ST+V50 = -14%) and Tmáx/ Mmáx ratios (ST = -30,3%, ST+V30 = -38,2%, ST+V50 = -28,1%) (p>0.05). However it was found a significant time effect for Tmáx/ Mmáx ratio (-48.9%) (p<0,05).CONCLUSION: A single strength training session induces a brief impairment on muscle spindle activity. This impairment is not greater if ST is combined with vibration. Performing ST on a vibration platform did not additionally increase QCSA, MDS and VJ performance compared with ST alone

A hipertrofia ventricular esquerda (HVE) é importante fator de risco cardiovascular. O objetivo deste estudo retrospectivo foi verificar a associação de critérios eletrocardiográficos de HVE com as características anatômicas e histológicas do coração, em 51 pacientes submetidos à necropsia. Procedeu-se à medição do diâmetro transverso dos cardiomiócitos e da porcentagem de fibrose do ventrículo esquerdo e direito. Entre os pacientes que apresentavam HVE anatômica, o critério de Romhilt foi positivo em 92,3%, sendo superior aos demais critérios avaliados, com especificidade de 89,5% e sensibilidade de 68,8%, Foi o único que se associou a características anatômicas e histológicas do coração / The left ventricular hypertrophy (LVH) is an important cardiovascular risk factor. The purpose of the present retrospective paper is to examine the association of LVH electrocardiographic criteria with both anatomical and histological characteristics of the heart on 51 patients submitted to the necropsy. The study carried out the measurement of the transverse diameter of cardiomyocytes, as well as the percentage of fibrosis at both left and right ventriculi. Among those patients who presented anatomic LVH, the Romhilt criterium resulted positive in 92.3% of the cases, thus surpassing the other criteria evaluated, with specificity and sensibility up to 89.5% and 68.8% respectively. This was the only criterium associated to both anatomic and histological characteristics of the heart

L’obésité et le surpoids ont été décrits comme une pandémie. L’obésité et le vieillissement vont conduire à des complications cardiovasculaires. De plus, l’obésité favoriserait un vieillissement cardiaque prématuré chez les adultes jeunes. L’hypothèse de ce travail est qu’un régime riche en graisses, démarré avant l’âge adulte, poursuivi sur une longue durée, pourrait entraîner un vieillissement « accéléré » cardiovasculaire et métabolique. Nous avons démontré, dans un modèle murin vieillissant, qu’un régime riche en graisses conduit à des troubles métaboliques ainsi qu’à une augmentation de la masse grasse et à une détérioration du métabolisme au niveau du tissu adipeux blanc. Ces troubles sont associés à des altérations au niveau cardiaque, malgré l’absence de modifications de la pression artérielle et de la fréquence cardiaque. Le vieillissement, chez les souris obèses, va conduire à un remodelage du ventricule gauche accompagné par une dysfonction systolique. Au niveau tissulaire cardiaque, le vieillissement et le régime précoce conduisent à l’augmentation de l’expression de gènes de fibrose confirmant ainsi le phénotype hypertrophique. Le vieillissement associé à un régime riche en graisses précoce conduit également à une up-régulation de GDF11. GDF11 peut alors être considéré comme un marqueur de vieillissement cardiaque accéléré. Ces résultats peuvent suggérer des voies thérapeutiques ou préventives, où l’inhibition de GDF11 améliorerait le pronostic et la survie cardiovasculaire des sujets obèses. L’étude de ce modèle nous a ainsi permis de mettre en évidence qu’un régime riche en graisses conduit à un vieillissement accéléré au niveau cardiaque / Obesity and being overweight have been described as a global pandemic. Both obesity and aging will lead to cardiovascular complications. In addition, it has been highlighted that obesity promotes premature cardiac aging in young adults. The hypothesis of this work is that a high fat diet begun before adulthood, pursued over a long period of time, could lead to “accelerated” cardiovascular and metabolic aging. We have demonstrated, in an aging mouse model, that an early high fat diet leads to metabolic disorders and to an increase in fat mass and a deterioration in metabolism of white adipose tissue. These disorders are associated with alterations in cardiac morphology and function, despite an absence of changes in blood pressure and heart rate. Ageing, in obese mice, leads to ventricular remodeling accompanied by systolic dysfunction. In cardiac tissue, aging and early diet lead to an increased expression of fibrosis genes confirming the hypertrophic phenotype. Aging associated with an early high fat diet led also to an up-regulation of GDF11. GDF11 may then be considered as a marker of accelerated cardiac aging. These results may suggest therapeutic or preventive pathways, where inhibition of GDF11 improves prognosis and survival in obese subjects with cardiovascular disease. The study of this model has allowed us to demonstrate that a high fat diet leads to accelerated aging at the level of the heart

Background: Recent research has demonstrated the presence of heat being an effective stimulus for increasing skeletal muscle and strength. The exposure of increased environmental temperature combined with resistance training has been shown to amplify muscle adaptation for hypertrophy and strength. However, research into the potential effects of using heat stress combined with resistance training to increase performance criteria, such as speed and agility, are minimal. Utilizing a hot environment coupled with an intense exercise regime has been considered as a potential aid for sport preparation given the evidence that heat stress has on promoting hypertrophy and strength. The desired result is to enhance athletic performance. Aim: The aim of this study was to examine if (a) performing resistance training in a hot environment for 10 weeks induces greater increases in muscle mass and (b) whether this combination improves performance in speed, agility and strength compared to resistance training in a standard temperate environment. Methods: 17 healthy male adults, who have undergone a consistent regime of resistance training in the six months leading up to the study, were distributed at random into two groups; (1) Intervention group (Heat n=8) training in 40°C and (2) control group (Con, n=9) training in 23°C. Each group would follow a 10-week resistance exercise protocol. To monitor time-course adaptations, lean body mass, speed, agility and strength were measured at baseline, week 5 and week 10. Results: Over the selected training period, there was no statistically significant difference observed between the two groups or time x group interaction, over the 10-week exercise duration with respect to lean body mass, speed, agility or strength. Conclusion: Compared to the resistance training regime in the standard temperature condition of 23°C (group two), training results suggest heat stress in the hot environment at 40°C (group one) had no effective stimulus in amplifying hypertrophic adaptations in skeletal muscle nor in increasing performance in speed, agility or strength. Certain hypothetical factors were implicated for heat stress being ineffective such as potential counter-productive aspects from heat exposure or flawed methodology. / Heat Effects on Adaptations to Resistance Training, Victoria University

Introdução: A hipertrofia cardíaca induzida por sobrecarga hemodinâmica crônica (HC) é caracterizada por espessamento das paredes do ventrículo esquerdo e do tecido intersticial. As atividades aumentadas de calpaína-1 e metaloproteinase de matriz(MMP)-2 são observadas em diferentes modelos de hipertensão arterial e estão relacionadas com as mudanças fisiopatológicas na HC. Por outro lado, a atividade de MMP-2 parece ser modulada positivamente por ativação de calpaína-1 em diferentes modelos. O objetivo deste trabalho é analizar se a calpaína-1 contribui para o aumento da atividade de MMP-2 no coração e se esse mecanismo resulta nas mudanças crônicas cardíacas na hipertensão renovascular. Métodos: Ratos Wistar submetidos ao modelo de 2-rins-1 clipe (2R-1C)(180-200g) e seus respectivos controles (Sham) foram tratados com verapamil (VRP), um bloqueador de canais para cálcio tipo L (BCCL, 8mg/kg/bid) ou veículo durante 8 semanas. O BCCL reduz as concentrações intracelulares de cálcio, o que leva à diminuição da ativação de calpaína-1, e então à possível modulação da atividade e expressão proteica de MMP-2. Pressão arterial sistólica (PAS) dos ratos foi monitorada durante 10 semanas de hipertensão por pletismografia de cauda. O ventrículo esquerdo (VE) foi analisado por histologia e ecocardiografia para avaliação das dimensões ventriculares. A atividade de calpaína-1 e MMP-2 foi avaliada por zimografia em gel. A expessão proteica de calpaína-1 e MMP-2 foi avaliada por western blot e imunofluorescência. Os corações foram submetidos à avaliação funcional por Langendorff. Todos os protocolos foram aprovados pelo Comitê de Ética em Pesquisa Animal da Faculdade de Medicina de Ribeirão Preto (43/2017). Resultados: Após 10 semanas, a PAS teve um aumento sustentado nos animais 2R-1C e o tratamento com VRP não foi capaz de reduzí-la em nenhum tempo de hipertensão. O peso corporal não apresentou diferença significativa entre os grupos. O grupo hipertenso teve um aumento da massa cardíaca quando comparado ao sham e o tratamento com verapamil reduziu esse parâmetro. A análise da espessura do ventrículo esquerdo demonstra que o VRP é capaz de reverter a HC induzida por sobrecarga pressórica nos animais hipertensos. Os animais 2R-1C apresentaram um aumento singificativo na expressão proteica e atividade de calpaína-1 e o VRP foi capaz de diminuir esses níveis. Foi observado aumento da atividade das isoformas de MMP-2 nos ratos 2R-1C quando comparados aos controles e o VRP foi capaz de reduzir a atividade da isoforma de 64kDa. A contratilidade cardíaca intrínseca dos animais 2R-1C sugere uma disfunção cardíaca quando comparados aos controles sham, embora a fração de ejeção desses animais esteja preservada. O VRP não foi capaz de alterar esses parâmetros. Conclusão: O VRP pode contribuir para a redução da hipertrofia cardíaca por diminuir a expressão proteica de calpaína-1 e MMP-2 na hipertensão renovascular. Apoio financeiro: Capes, CNPq, FAPESP / Introduction: The chronic hemodynamic overload-induced cardiac hypertrophy (CH) is characterized by thickening of the left ventricle walls and hypertrophy of the cardiomyocytes and interstitial tissue. Increased activity of calpain-1 and matrix metalloproteinase(MMP)-2 was observed in different models of arterial hypertension models and contributes to the pathophysiologic changes shown in CH. On the other hand, MMP-2 activity is also positively modulated by activation of calpain-1 in different animal models of cardiovascular diseases. The objectives here are to analyze whether calpain-1 contributes to increase the activity of MMP-2 in the heart and whether this mechanism results in chronic cardiac changes in the renovascular hypertension. Methods: Two kidney-one clip (2K1C) hypertensive male Wistar rats (180-200g) and their respective controls (Sham) were orally treated with verapamil (VRP), a L-type calcium channels blocker (LCCB, 8mg/kg/bid), or vehicle during 8 weeks. The LCCB reduces the intracellular concentration of calcium, thus decreasing the activation of calpain-1, and then may modulate the activity of MMP-2. Systolic blood pressure (SBP) was monitored in the rats during 10 weeks of hypertension. Left ventricle (LV) was analyzed by histology and echocardiography to evaluate ventricle thickening. Calpain- 1 and MMP-2 activities were analyzed by zymography and their expression by immunofluorescence and western blot. Hearts were submitted to functional evaluation by Langendorff. All the protocols were approved by the Ethical Committee in Animal Research of Ribeirao Preto Medical School (43/2017). Results: After 10 weeks, the systolic blood pressure had sustained increase and treatment with VRP was not able to decrease it in any time of hypertension. The body weight did not present significant changes between the groups. Hypertensive group had significant increase in the ventricle/body weight ratio (VW/BW) when compared to sham and treatment with VRP decreased it. Analysis of ventricle thickening showed that VRP is able to revert CHinduced pressure overload. The 2K-1C rats showed a significant increase in the activity and expression of calpain-1 in the heart and VRP reverted it. It was also observed increased activity of MMP-2 forms in the hypertensive rats and VRP decreased the 64kDa MMP-2 activity. The 2K-1C group had cardiac dysfunction when compared to controls groups, and VRP did not alter it. The ejection fraction was not changed in 2K- 1C rats. Conclusion: VRP decreased expression and activity of calpain-1 and MMP-2 in the hearts of 2K-1C rats and then contributed to ameliorate hypertension-induced cardiac hypertrophy

O efeito da hipertrofia induzida por sobrecarga funcional no músculo extensor digital longo (EDL) e sóleo de ratos diabéticos induzidos por estreptozotocina foi avaliado. Ratos Wistar foram induzidos ao estado diabético por dose única de estreptozotocina (65mg/kg peso corporal, i.v.) e mantidos nessa condição durante quatro semanas. Foi então realizada tenotomia do músculo gastrocnêmio ou ablação do músculo tibial anterior. Os conteúdos de Akt e S6 totais e fosforiladas foram avaliados após uma e quatro semanas de sobrecarga nos músculos EDL e sóleo. No EDL, após 7 dias de sobrecarga, ocorreu aumento de fosfo-Akt, fosfo-S6 e S6 total no músculo EDL nos grupos diabético e controle. Os aumentos foram semelhantes entre os grupos. No músculo sóleo, os conteúdos de Akt total e fosfo-Akt aumentaram significativamente, após 7 dias de sobrecarga funcional. A área da secção transversa das fibras, a massa, as forças tetânica e isotônica, absolutas e específicas foram avaliadas nos músculos sóleo e EDL após 4 semanas de sobrecarga e apresentaram aumentos similares em resposta à sobrecarga funcional. A deficiência de insulina por até 4 semanas não afeta de modo significativo a resposta hipertrófica induzida por sobrecarga funcional nos músculos sóleo e EDL de ratos. / The effect of hypertrophy induced by functional overload on extensor digitalis longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats were evaluated. Male Wistar rats were rendered diabetic by a single dose of streptozotocin (65mg/kg b.w., i.v.) and maintained under this condition for four weeks. Then, tenotomy of the gastrocnemius muscle or tibialis anterior ablation were performed. Contents of total and phosphorylated Akt and S6 were evaluated after one and four weeks of overload on EDL and soleus muscles. Phospho-Akt content was increased in control and diabetic animals in hypertrophied muscles. Contents of phospho-S6 and total S6 increased after 7 days of overload either in the control and diabetic groups. In soleus muscle, after 7 days of overload, increases in contents of total Akt and phospho-Akt were observed. Content of phospho-S6 was increased in diabetic group. Fiber cross-sectional area (CSA), muscle mass, and tetanic forces were evaluated after four weeks of overload. Increases in muscle mass and CSA were observed in EDL and soleus muscles of diabetic and control rats. Deficiency of insulin for up to 4 weeks has no significant effect on the hypertrophic response induced by functional overload on the EDL and soleus muscles.

Do ponto de vista clínico, o remodelamento ventricular está associado a um pior prognóstico. Pacientes com remodelamento já diagnosticado, ou com alto risco de desenvolvê-lo, devem ser tratados de forma intensiva, a fim de prevenir, atenuar ou mesmo reverter esse processo. O objetivo do presente estudo foi investigar os efeitos da vitamina E associada a nanopartículas lipídicas no remodelamento cardíaco, em ratos. Medidas ecocardiográficas foram determinadas 24 horas pós infarto e seis semanas após tratamento. Cortes teciduais do coração foram submetidos a coloração com Hematoxilina eosina e Picrosirius red. Duas regiões distintas do ventrículo esquerdo remotas ao infarto foram examinadas: subendocárdica e não subendocárdica. A extensão do infarto, o diâmetro dos miócitos, a fração de variação da área e o índice de expansão do ventrículo esquerdo foram determinados. No ecocardiograma observamos que os grupos infartados apresentaram um aumento no diâmetro diastólico e sistólico, uma diminuição da fração de encurtamento e da fração de variação da área quando comparados ao grupo controle. Na análise morfométrica, foi observado que nos animais infartados houve um aumento do diâmetro dos miócitos, da expansão do ventrículo esquerdo e da fração de volume do colágeno, principalmente na região subendocárdica, quando comparado ao grupo controle. A vitamina E associada a nanopartículas lipídicas, não apresentou efeitos protetores e nem atenuantes no remodelamento cardíaco nesse modelo experimental / From a clinical point of view, the ventricular remodeling is associated with a worse prognosis. Patients already diagnosed remodeling or at high risk of developing it, should be treated intensively to prevent, attenuate or even reverse this process. The aim of this study was to investigate the effects of vitamin E associated with lipid nanoparticles on cardiac remodeling in rats. Echocardiographic measurements were determined 24 hours post infarction and six weeks after treatment. Heart tissue sections were stained with Hematoxylin eosin and Picrosirius red. Two distinct regions of the left ventricle, remote to infarction, were examined: subendocardial and not subendocardial. The extent of the infarction, the diameter myocytes, collagen volume fraction and expansion index of the left ventricle were determined. On echocardiogram we observed that infarcted groups showed an increase in diastolic and systolic diameter and decreased in fractional shortening and the area variation fraction when compared to the control group. In the morphometric analysis, was observed that in infarcted animals there was an increase in the diameter myocytes, the expansion of the left ventricle and collagen volume fraction, especially in the subendocardial region, when compared to the control group. Vitamin E associated to lipid nanoparticles, showed no protective nor attenuated effects on cardiac remodeling in this experimental model