Myocardial proteome changes in aortic stenosis rats subjected to long-term aerobic exercise.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure.

We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.

Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis.

Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca2+ handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; n = 61) and aortic stenosis (AoS; n = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca2+ concentrations were evaluated. The expression of regulatory proteins for diastolic Ca2+ was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca2+ channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca2+ and improved the cellular Ca2+ influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure.

In pathological cardiac hypertrophy, the heart is more dependent on glucose than fatty acids. This shift in energy metabolism occurs due to several factors, including the oxygen deficit, which activates hypoxia-inducible factor-1α (HIF-1α), a critical molecule related to glucose metabolism. However, there are gaps regarding the behavior of key proteins in the glycolytic pathway and HIF-1α during the transition from hypertrophy to heart failure (HF). This study assesses the hypothesis that there is an early change and enhancement of HIF-1α and the glycolytic pathway, as well as an association between them during cardiac remodeling. Sham and aortic stenosis Wistar rats were analyzed at 2, 6, and 18 weeks and in HF (n = 10-18). Cardiac structure and function were investigated by echocardiogram. Myocardial glycolysis, the aerobic and anaerobic pathways and glycogen were analyzed by enzymatic assay, Western blot, and enzyme-linked immunosorbent assay (ELISA). The following were observed: increased left ventricular hypertrophy; early diastolic function change and severe systolic and diastolic dysfunction in HF; increased HIF-1α in the 2nd week and in HF; precocious alteration and intensification of glycolysis with a shift to anaerobic metabolism from the 6th week onwards; association between HIF-1α, glycolysis, and the anaerobic pathway. Our hypothesis was confirmed as there was an early change and intensification in glucose metabolism, alteration in HIF-1α, and an association between data during the progression from hypertrophy to heart failure.

The Dysfunctional Scenario of the Major Components Responsible for Myocardial Calcium Balance in Heart Failure Induced by Aortic Stenosis. / Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica.

BACKGROUND: Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. OBJECTIVE: To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. METHODS: Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. RESULTS: Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. CONCLUSION: Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.

FUNDAMENTO: O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. OBJETIVO: Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. MÉTODOS: Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p <0,05. RESULTADOS: Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+. CONCLUSÃO: Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.

Metodologias de ensino do karatê-do shotokan para crianças / Shotokan karatê teaching methodologies for children / Metodologías para enseñar karate-do skhotokan a niños

O presente artigo tem como objetivo, caracterizar as diferentes metodologias de ensino do Karatê-Do Shotokan para crianças. Utilizando-se de uma pesquisa realizada de forma indireta, por meio de uma revisão bibliográfica. Onde encontrou-se, que as lutas são manifestações elementares da cultura corporal, sofrendo ao longo do tempo constantes modificações, culminando no surgimento de inúmeras lutas ou artes marciais. Entre elas o Karatê-Do Shotokan, tendo como forma tradicional de ensino os três K, pautado no método analítico. Entretanto, no processo de ensino torna-se importante permitir conhecimentos da ciência e da pedagogia do esporte, através das dimensões do ensino e de métodos de ensino global das lutas. E concluiu-se, que para a evolução das crianças no Karatê-Do Shotokan é necessário se pensar em mecanismos pedagógicos, com objetivos claros e concretos, utilizando dos métodos parcial e global, fundamentados nas dimensões do ensino.

This article aims to characterize the different teaching methodologies of Karate-Do Shotokan for children. Using an indirect research, through a bibliographic review. Where it was found, that fights are elementary manifestations of body culture, undergoing constant changes over time, culminating in the emergence of numerous fights or martial arts. Among them the Karate-Do Shotokan, having the three K as a traditional teaching method, based on the analytical method. However, in the teaching process it is important to allow knowledge of science and sport pedagogy, through the dimensions of teaching and methods of global teaching of struggles. And it was concluded that for the evolution of children in Karate-Do Shotokan it is necessary to think about pedagogical mechanisms, with clear and concrete objectives, using partial and global methods, based on the dimensions of teaching.

Este artículo tiene como objetivo caracterizar las diferentes metodologías de enseñanza del Karate-Do Shotokan para niños. Mediante una investigación indirecta, a través de una revisión bibliográfica. Donde se encontró, que las peleas son manifestaciones elementales de la cultura corporal, que experimentan cambios constantes a lo largo del tiempo, culminando con el surgimiento de numerosas peleas o artes marciales. Entre ellos el Karate-Do Shotokan, que tiene las tres K como método de enseñanza tradicional, basado en el método analítico. Sin embargo, en el proceso de enseñanza es importante permitir el conocimiento de la pedagogía científica y deportiva, a través de las dimensiones de la enseñanza y los métodos de enseñanza global de las luchas. Y se concluyó que para la evolución de los niños en Karate-Do Shotokan es necesario pensar en mecanismos pedagógicos, con objetivos claros y concretos, utilizando métodos parciales y globales, basados en las dimensiones de la enseñanza.

Adjustments in ß-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis.

BACKGROUND/AIMS: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive ß-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through ß-adrenergic signaling preservation. METHODS: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. RESULTS: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The ß2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the ß-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during ß-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. CONCLUSION: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the ß-adrenergic responsiveness, which reveals that the adjustments in ß-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats.

Cardioprotection Generated by Aerobic Exercise Training is Not Related to the Proliferation of Cardiomyocytes and Angiotensin-(1-7) Levels in the Hearts of Rats with Supravalvar Aortic Stenosis.

BACKGROUND/AIMS: The beneficial effect of aerobic exercise training (ET) on cardiac remodeling caused by supravalvar aortic stenosis (AS) has been demonstrated in experimental studies; however, the mechanisms responsible for improving cardiac function are not entirely understood. We evaluated whether ET-generated cardioprotection in pressure-overloaded rats is dependent on cardiomyocyte proliferation, increased angiotensin-(1-7) (Ang-1-7) levels, and its receptor in the myocardium. METHODS: Eighteen weeks after ascending AS surgery, Wistar rats were randomly assigned to four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed) and exercised aortic stenosis (AS-Ex) groups. The moderate treadmill exercise protocol was performed for ten weeks. The functional capacity was assessed by treadmill exercise testing. Cardiac structure and function were evaluated by echocardiogram. Cardiomyocyte proliferation was evaluated by flow cytometry. Expression of cell cycle regulatory genes as CCND2, AURKB, CDK1, and MEIS1 was verified by RT-qPCR. Cardiac and plasma angiotensin I (Ang I), angiotensin II (Ang II), and Ang-(1-7) levels were analyzed by high-performance liquid chromatography (HPLC). The angiotensin-converting enzyme (ACE) activity was assessed by the fluorometric method and protein expression of AT1 and Mas receptors by Western blot. RESULTS: The AS-Ex group showed reduced left ventricular wall relative thickness and improved ejection fraction; also, it showed decreased gene expression of myocyte cell cycle regulators, ACE, Ang I, Ang II and Ang II/Ang-(1-7) ratio levels compared to AS-Sed group. However, ET did not induce alterations in Ang-(1-7) and cardiac Mas receptor expression and myocyte proliferation. CONCLUSION: Aerobic exercise training improves systolic function regardless of myocyte proliferation and Ang-(1-7)/Mas receptor levels. However, the ET negatively modulates the vasoconstrictor/hypertrophic axis (ACE/Ang II) and decreases the expression of negative regulatory genes of the cell cycle in cardiomyocytes of rats with supravalvular aortic stenosis.

Increased angiotensin II from adipose tissue modulates myocardial collagen I and III in obese rats.

It has been described that the cardiac dysfunction in the obesity model is because of collagen imbalance and that angiotensin II (Ang II) contributes to myocardial fibrosis. However, it remains undefined if changes in collagen I and III metabolism in obesity is due to the renin-angiotensin system (RAS) dysregulation from myocardium or excessive adipose tissue. AIM: This study aimed to verify whether the changes in myocardial collagen metabolism result from RAS deregulation of cardiac or adipose tissue in an obesity model. MAIN METHODS: Wistar rats were fed with control (CD) and high-fat (HFD) diets for 30 weeks. After the dietary intervention, animals were assigned to be treated with losartan at the 30 mg/kg/day dosage or kept untreated for an additional five weeks. KEY FINDINGS: HFD induced obesity, comorbidities, and cardiac collagen overexpression. The HFD group presented an increase in Ang II levels in both adipose tissue and plasma, as well as AT1 receptor expression in cardiac tissue. Of note, the myocardial Ang II was not changed in the HFD group. Losartan administration reduced some obesity-induced comorbidities regardless of weight loss. The AT1 receptor blockade also decreased the release of Ang II from adipose tissue and myocardial AT1 receptor and collagen. SIGNIFICANCE: It was seen that excessive adipose tissue is responsible for the exacerbated circulating Ang II, which induced cardiac fibrosis development.

Myocardial Dysfunction after Severe Food Restriction Is Linked to Changes in the Calcium-Handling Properties in Rats.

Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca2+-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar-Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca2+ and in the absence or presence of a sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) specific blocker. The expression of Ca2+-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca2+ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats.

Prevalence of overweight and obesity in elementary school students of Vitória, ES / Prevalência de sobrepeso e obesidade em escolares do ensino fundamental de Vitória/ES

Although numerous studies have analyzed overweight and obesity among schoolchildren from various Brazilian regions, the data relative to the state of Espírito Santo (ES) remains scarce. Considering the information presented, the purpose of present study was to investigate the prevalence of overweight and obesity among elementary school students from Vitória, ES. This was a cross-sectional study including 572 school children between 7 to 14 years old enrolled in municipal elementary schools in Vitória, ES, totalling 310 girls and 262 boys, who were randomly selected by stratified cluster sampling. The prevalence of overweight and obesity was calculated based on the children's anthropometric profile according to percentage of body fat by measuring skinfold thickness and body mass index (BMI). Based on BMI, the prevalence of overweight was high in both sexes, with 20.6% among the boys and 20.9% among the girls. The prevalence of obesity did not differ between boys and girls, with 6.5% and 7.7%, respectively. The results of the skin-fold thickness of skin show that 31.3% of children attending municipal schools in Vitória/ES were classified as overweight. In summary, the current study found a high prevalence of overweight and obesity, reaffirming that the overweight reaches a significant proportion of children and adolescents who attend public elementary schools in the city of Vitória, ES

Embora numerosos estudos tenham analisado o sobrepeso e a obesidade entre escolares de várias regiões brasileiras, dados relativos ao estado do Espírito Santo (ES) ainda são escassos. Considerando as informações destacadas acima, o objetivo do presente estudo foi investigar a prevalência de sobrepeso e obesidade em crianças do ensino fundamental de Vitória/ ES. Estudo transversal com 572 escolares de 7 a 14 anos matriculados em escolas municipais do ensino fundamental de Vitória/ES, totalizando 310 meninas e 262 meninos, selecionados aleatoriamente por amostra de estratificada por conglomerados. A prevalência de sobrepeso e obesidade foi calculada com base no perfil antropométrico das crianças de acordo com a porcentagem de gordura corporal, medindo-se a espessura das dobras cutâneas e o índice de massa corporal (IMC). Com base no IMC, a prevalência de excesso de peso foi alta em ambos os sexos, com 20,6% entre os meninos e 20,9% entre as meninas. Os resultados da espessura da prega cutânea demonstram que 31,3% das crianças que frequentavam escolas municipais em Vitória/ES foram classificadas com excesso de peso. Em conclusão, o presente estudo encontrou alta prevalência de sobrepeso e obesidade, reafirmando que o excesso de peso atinge uma proporção significativa das crianças e adolescentes que frequentam escolas municipais em Vitória / ES

Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model.

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling.

Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance.

Cardiac remodeling (CR) is a structural change of the heart due to chronic hemodynamic overload related to changes in both myocyte and extracellular matrix (ECM). We investigated that the imbalance of collagen V promotes cardiomyocyte apoptosis that contributes to heart failure and cell death. Aortic stenosis was induced surgically and male Wistar rats were randomized to 18 weeks (Sham 18 w, n = 12; AoS 18 w, n = 12) and severe of heart failure (Sham HF, n = 12; AoS HF, n = 12) groups. Functional and structural echocardiogram, immunohistochemistry for Ki-67, TUNEL assay and Immunofluorescence for collagen were performed. Our main results were: (1) Progressive reduction of cardiac functional capacity due to cardiac remodeling with decreased eject fraction in heart failure; (2) Imbalance of collagen deposition with increased, crowded and irregular collagen I in situ expression; (3) Dysregulation of dynamic control of collagen fibers with exposed epitopes of collagen V; (4) Additional apoptosis that are dependent to cardiac injury. The collagen V expression in cardiac remodeling is for the first time described and may be related to additional apoptosis and autoimmune response. Our findings suggest a critical role of collagen V in cardiac remodeling to modulate and promote heart failure and death.

Influência da exposição à fumaça de cigarro e dotreinamento físico no apetite e desenvolvimentocorporal em ratos / Influence of exposure to cigarette smoke and physical training inappetite and body development in rats

O fumo apresenta potencial para promover alterações no sistema hormonal, apetite e, consequentemente, na ingestãoalimentar. Por sua vez, o treinamento físico amplia a demanda metabólica, exerce efeito substancial sobre o balançoenergético. Objetivou-se verificar a influência do tabagismo e do treinamento físico no apetite e no desenvolvimentodo peso corporal em ratos. Utilizou-se ratos Wistar (n=40, entre 200g e 250g) distribuídos em quatro grupos: Controle(C); Controle Treinado (CT); Exposto (E); Treinado/Exposto (TE). A exposição à fumaça de cigarro (EFC) e treinamento(natação) durou 15 semanas. Os animais foram pesados semanalmente e a ingestão alimentar pesada diariamente.Analisou-se com ANOVA de duas vias e adotou-se nível de significância de 5%. A ingestão nos ratos EFC foi menor,comparado com os não EFC (p=0,001). Os ratos treinados apresentaram menores valores na ingestão em relação aosnão treinados (p=0,044). A interação estatística entre os fatores (fumo e natação) interferiu na ingestão (p=0,013). Ascurvas de crescimento apresentaram valores inferiores de peso corporal nos grupos EFC. Houve interação estatísticaentre os fatores fumo e natação para o peso corporal (p=0,046). Ocorreu diferença estatística com maiores valores paraos pesos do coração, pulmão e tíbia nos grupos não EFC, em comparação aos ratos EFC. Conclui-se que a EFC inibeo apetite e promove prejuízo no desenvolvimento corporal. E, o treinamento físico apresenta influência no balançoenergético negativo cronicamente, com diminuição no ganho de peso. Porém, não interfere no desenvolvimentocorporal, sendo benéfico diferentemente da exposição à fumaça de cigarro.

The tobacco has the potential to cause changes in the hormonal system, appetite and therefore food intake. In turn,physical training increases metabolic demand, exerts a substantial effect on the energy balance. This study aimed toverify the influence of smoking and physical training in appetite and the development of body weight in rats. Rats Wistarwere used (n=40, between 200g and 250g) rats were distributed into four groups: control (C); Trained control (TC);Exposure (E); Trained / exposure (TE). Exposure to cigarette smoke (ECS) and training (swimming) lasted 15 weeks.The animals were weighed weekly and food intake weighed daily. Analyzed with two-way ANOVA and was adopteda significance level of 5%. The ECS intake in rats was lower compared to the non ECS (p=0.001). The trained ratshad lower values in intake compared to untrained (p=0.044). The statistical interaction between factors (smoking andswimming) interfered with the intake (p=0.013). The growth curves showed lower body weight in the groups ECS. Wasno statistical interaction between smoking and factors swimming to body weight (p=0.046). Statistical difference withhigher values for the weights of the heart, lung, and tibia in group no ECS, compared to rats ECS. We conclude that ECSinhibits appetite and promotes loss in body development. And, physical training has chronically negative influence onenergy balance, with reduction in weight gain. However, it does not interfere with body development, and beneficialunlike exposure to cigarette smoke.

Cardiac Dysfunction Induced by Obesity Is Not Related to ß-Adrenergic System Impairment at the Receptor-Signalling Pathway.

Obesity has been shown to impair myocardial performance. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them beta-adrenergic (ßA) system, an important mechanism of regulation of myocardial contraction and relaxation. The objective of present study was to evaluate the involvement of ßA system components in myocardial dysfunction induced by obesity. Thirty-day-old male Wistar rats were distributed in control (C, n = 25) and obese (Ob, n = 25) groups. The C group was fed a standard diet and Ob group was fed four unsaturated high-fat diets for 15 weeks. Cardiac function was evaluated by isolated papillary muscle preparation and ßA system evaluated by using cumulative concentrations of isoproterenol and Western blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats and several comorbidities; however, were not associated with changes in systolic blood pressure. Obesity caused structural changes and the myocardial responsiveness to post-rest contraction stimulus and increased extracellular calcium (Ca2+) was compromised. There were no changes in cardiac function between groups after ßA stimulation. The obesity was not accompanied by changes in protein expression of G protein subunit alpha (Gsα) and ßA receptors (ß1AR and ß2AR). In conclusion, the myocardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to ßAR system impairment at the receptor-signalling pathway.

Training and cardiovascular responses from cigarette smoke exposure.

The aim of this study was to evaluate the early effect of the endurance training (ET) on systolic blood pressure (SBP), heart rate (HR) and rate pressure-product (RPP) after acute cigarette smoke exposure. Twenty male Wistar rats were randomly allocated into two groups: trained (TEx; n = 10) and control (CEx; n = 10), exposed to smoke. TEx rats undertook ET during 2 weeks (swimming, 5 days/week; 1 h/session) and CEx group was kept in sedentary lifestyle. After ET protocol both groups were exposed to cigarette smoke only once (total 1 h; 2 × 30 min with interval of 10 min between exposures; rate of 10 cigarettes/30 min). SBP, HR and RPP were measured after 2 weeks and just after (5 min) acute cigarette smoke (tail plethysmograph). All parameters did not differ (P > 0.05) between TEx (RPP = 45018 ± 1970 mmHg/bpm) and CEx (43695 ± 2579 mmHg/bpm) after ET protocol. However, all cardiovascular parameters increased (P < 0.05) only for CEx just after the cigarette smoke exposure. We concluded that ET can attenuate the aggression from acute smoking to cardiovascular system, with a few days of training and even with no chronic effect on these parameters at basal condition.