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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.

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.

Resumo 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

Hypertension is a chronic disease considered an important risk factor to high level of morbidity and mortality in the world. The objective was to evaluate the prevalence of hypertension and cardiovascular risk factors in Sinop (MT/Brazil). This cross-sectional study was conducted in 2014 between February and November. Data collection included self-reported behavioral risk factors and clinical measurements comprising blood pressure and anthropometry, totaling 649 adult subjects. The prevalence of hypertension was 39%, being higher in men (23%) than women (16%). Overall, 33.4% were obese and 39.9% were overweight; 12.5% smoke one or more packs of cigarettes per day; 68.9% were sedentary; 50.5% demonstrated altered waist/hip ratio; 22.8% and 50.8%, respectively, presented high and very high cardiovascular risk by waist circumference measure. Odds ratio analyses demonstrated that hypertension was associated with male subjects, increased age, excess weight and high waist/hip ratio as well altered waist circumference. This study showed high prevalence of hypertension, overweight and obesity in Sinop/MT. In addition, many hypertensive patients under anti-hypertensive treatment showed uncontrolled blood pressure levels. There was a significant association between hypertension and age, gender, body mass index, waist circumference and waist/hip ratio.

Made available in DSpace on 2020-12-12T01:48:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Obesity is a pandemic associated with a high incidence of cardiovascular disease; however, the mechanisms are not fully elucidated. Proteomics may provide a more in-depth understanding of the pathophysiological mechanisms and contribute to the identification of potential therapeutic targets. Thus, our study evaluated myocardial protein expression in healthy and obese rats, employing two proteomic approaches. Male Wistar rats were established in two groups (n = 13/group): control diet and Western diet fed for 41 weeks. Obesity was determined by the adipose index, and cardiac function was evaluated in vivo by echocardiogram and in vitro by isolated papillary muscle analysis. Proteomics was based on two-dimensional gel electrophoresis (2-DE) along with mass spectrometry identification, and shotgun proteomics with label-free quantification. The Western diet was efficient in triggering obesity and impaired contractile function in vitro; however, no cardiac dysfunction was observed in vivo. The combination of two proteomic approaches was able to increase the cardiac proteomic map and to identify 82 differentially expressed proteins involved in different biological processes, mainly metabolism. Furthermore, the data also indicated a cardiac alteration in fatty acids transport, antioxidant defence, cytoskeleton, and proteasome complex, which have not previously been associated with obesity. Thus, we define a robust alteration in the myocardial proteome of diet-induced obese rats, even before functional impairment could be detected in vivo by echocardiogram. Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Centre for Proteome Research Institute of Integrative Biology University of Liverpool Liverpool Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP) Center for the Study of Venoms and Venomous Animals (CEVAP)/Graduate Program in Tropical Diseases (FMB) São Paulo State University (UNESP) Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP) Center for the Study of Venoms and Venomous Animals (CEVAP)/Graduate Program in Tropical Diseases (FMB) São Paulo State University (UNESP) FAPESP: 2014/22152-0 FAPESP: 2015/16934-8 FAPESP: 2017/09688-6

Made available in DSpace on 2021-06-25T15:02:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Mato Grosso Research Foundation (FAPEMAT), Brazil Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background. Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. Aim of the study. We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. Methods. Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-alpha and IL-6 levels were measured by ELISA. Results. Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. Conclusions. Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function. (C) 2020 IMSS. Published by Elsevier Inc. Fed Univ Mato Grosso UFMT, Inst Hlth Sci, Ave Alexandre Ferronato 1200, BR-78556267 Sinop, Mato Grosso, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Internal Med, Botucatu, SP, Brazil Sao Paulo State Univ, Botucatu Sch Med, Dept Pathol, Botucatu, SP, Brazil Mato Grosso Research Foundation (FAPEMAT), Brazil: 161294/2014 CNPq: 442979/2014-2

Resumo Fundamento A obesidade é um fator de risco para complicações médicas, incluindo o sistema cardiovascular. Há informações limitadas sobre o colágeno no coração obeso. Nosso estudo anterior demonstrou uma redução dos níveis proteicos de colágeno miocárdico tipo I em ratos obesos alimentados com uma dieta com alto teor de gordura durante 34 semanas. No entanto, os mecanismos responsáveis pelos níveis baixos não estão completamente elucidados. Objetivo O objetivo deste estudo foi testar a hipótese de que a redução do colágeno tipo I está associada ao aumento da atividade da metaloproteinase-2 (MMP-2), a qual está ligada à elevação de leptina no miocárdio de ratos obesos. Métodos Ratos Wistar machos com 30 dias de idade foram randomizados em dois grupos: controle (dieta padrão) e obeso (dieta com alto teor de gordura), e alimentados durante 34 semanas. Foram avaliados as características gerais dos animais e os perfis metabólicos e endócrinos. Foram avaliados as expressões proteicas miocárdicas de colágeno tipo I, leptina e inibidores teciduais de metaloproteinases (TIMP), bem como a atividade da MMP-2. O teste de correlação de Pearson foi aplicado para determinar as associações entre variáveis. O nível de significância foi de 5%. Resultados Os animais obesos apresentaram índice de adiposidade mais elevado em comparação ao controle. Foram observadas comorbidades como intolerância à glicose, hiperinsulinemia, resistência à insulina, hiperleptinemia e hipertensão nos ratos obesos. A obesidade reduziu o colágeno tipo I, TIMP-1 e TIMP-2, e aumentou a leptina e a MMP-2 no miocárdio. Houve uma correlação negativa entre o colágeno tipo I e a MMP-2 e uma correlação positiva entre a leptina e a MMP-2. Conclusão Foi confirmada a hipótese de que a redução do colágeno tipo I está associada ao aumento da atividade da MMP-2 e da expressão de leptina no miocárdio de ratos obesos. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0) Abstract Background Obesity is a risk factor for medical complications, including the cardiovascular system. There is limited information on collagen in the heart in obesity. Our previous study showed decreased protein levels of myocardial collagen type I in obese rats fed a high-fat diet for 34 weeks. However, the mechanisms responsible for low levels are not fully elucidated. Objective The purpose of this study was to test the hypothesis that the reduction in collagen type I is associated with increased metalloproteinase-2 (MMP-2) activity, which is linked to elevated leptin in the myocardium of obese rats. Methods Thirty-day-old male Wistar rats were randomized into two groups, control (standard diet) and obese (high-fat diet), and fed for 34 weeks. The general animal characteristics and metabolic and endocrine profiles were evaluated. Myocardial protein expressions of collagen I, leptin, tissue inhibitors of metalloproteinases (TIMP), and MMP-2 activity were assessed. Pearson correlation was employed to determine the associations between variables. The level of significance was 5%. Results The obese animals had increased adiposity index compared to control. Comorbidities such as glucose intolerance, hyperinsulinemia, insulin resistance, hyperleptinemia, and hypertension were observed in obese rats. Obesity reduced collagen I, TIMP-1, and TIMP-2, and it increased leptin and MMP-2 in the myocardium. There was a negative correlation between collagen I and MMP-2 and a positive correlation between leptin and MMP-2. Conclusion The hypothesis was confirmed; the reduction in collagen type I is associated with increased MMP-2 activity and leptin expression in the myocardium of obese rats. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Made available in DSpace on 2020-12-12T02:14:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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 β-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 β-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 β2 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 β-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during β-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 β-adrenergic responsiveness, which reveals that the adjustments in β-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats. Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Institute of Health Science Federal University of Mato Grosso School of Physical Education and Sport University of São Paulo Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Biostatistics Institute of Biosciences of Botucatu São Paulo State University Department of Pathology Botucatu Medical School São Paulo State University Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) CAPES: 305399/2015-2 CAPES: 442822/2014-6

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.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.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 p0.05.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.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.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.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.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 p0,05.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+.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.

Made available in DSpace on 2020-12-12T02:05:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP), Botucatu Department of Morphology Institute of Biosciences São Paulo State University (UNESP), Botucatu Department of Pathology Botucatu Medical School São Paulo State University (UNESP), Botucatu Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP), Botucatu Laboratory of Biochemistry and Molecular Biology of the Exercise School of Physical Education and Sport University of São Paulo (USP) Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP), Botucatu Department of Morphology Institute of Biosciences São Paulo State University (UNESP), Botucatu Department of Pathology Botucatu Medical School São Paulo State University (UNESP), Botucatu Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP), Botucatu

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.

Made available in DSpace on 2020-12-12T02:02:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Cirrhotic cardiomyopathy is a condition where liver cirrhosis is associated with cardiac dysfunction. Triggers and blockers of cirrhotic cardiomyopathy are poorly understood, which might compromise the prognosis of chronic liver disease patients. We tested whether exercise training would reduce liver damage induced by thioacetamide and prevent liver cirrhosis-associated cardiomyopathy. Wistar rats were divided into three groups: control, thioacetamide (TAA), or TAA plus exercise. Thioacetamide increased liver weight and serum alanine aminotransferase and aspartate aminotransferase levels. Also, TAA treatment was involved with hepatic nodule formation, fibrotic septa, inflammatory infiltration, and hepatocyte necrosis. The exercise group presented with a reduction in liver injury status. We found that liver injury was associated with disordered cardiac hypertrophy as well as diastolic and systolic dysfunction. Exercise training attenuated cirrhosis-associated cardiac remodeling and diastolic dysfunction and prevented systolic impairment. These results provided insights that exercise training can mitigate cirrhotic cardiomyopathy phenotype. [Figure not available: see fulltext.]. Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Institute of Health Sciences Federal University of Mato Grosso (UFMT), Avenida Alexandre Ferronato, n°1200, Setor Industrial Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP) Department of Internal Medicine Botucatu School of Medicine São Paulo State University (UNESP), Botucatu Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP)

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&ndash, 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.

Made available in DSpace on 2022-04-28T19:44:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01 Purpose: To verify if the bark of Passiflora edulis prevents obesity-related disorders and oxidative stress in db/db mice. Methods: Obese male db/db mice (n = 14 animals) were randomly divided into two groups to receive standard chow and water (obese, n = 7 (OB)) or standard chow with bark of Passiflora edulis (BPe) (obese + BPe, n = 7 (OB + BPe)) for 16 weeks. The evaluated parameters in animals included food and caloric intake, body weight, total body fat and fat deposits, serum glucose, triglycerides, and total cholesterol. Malondialdehyde (MDA) and antioxidant capacity were evaluated in serum and organs (adipose tissue, kidney, liver, and heart). All groups were compared by Student t test, with p < 0.05. Results: The results showed the benefits from BPe by preventing abdominal fat deposition and by reducing the total cholesterol. Moreover, the compound increased the antioxidant capacity from the organs analyzed and reduced the MDA levels in the liver. Conclusion: It is possible to conclude that the consumption of the BPe prevents obesity-related disorders and oxidative stress in db/db mice. São Paulo State University (UNESP) Medical School São Paulo State University (UNESP) Institute of Biosciences São Paulo State University (UNESP) Medical School São Paulo State University (UNESP) Institute of Biosciences

Made available in DSpace on 2021-06-25T10:57:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Metabolic syndrome (MetS) include obesity as a critical feature and is strongly associated with risk of cardiovascular disease (CVD). Insights into mechanisms involved in the pathophysiology of these clinical manifestations are essential for the development of therapeutic strategies. Thus, Western diets (WD) have been widely employed in diet-induced obesity (DIO) model. However, there are variations in fat and sugar proportions of such diets, making comparisons challenging. We aimed to assess the impact of two types of the WD on metabolic status and cardiac remodeling, to achieve a DIO model that better mimics the human pathogenesis of MetS-induced CVD. Male Wistar rats were distributed into three groups: control diet, Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. Metabolic and inflammatory parameters and cardiac changes were characterized. WDF and WDS feeding promoted higher serum triglycerides, glucose intolerance, and insulin resistance, while just WDF presented inflammation in adipose tissue. WDF-fed rats showed increased catalase activity and malondialdehyde (MDA) and carbonyl protein levels, suggesting cardiac oxidative stress, while WDS-fed rats only raised MDA. Both WD equally elevated protein expressions involved in lipid metabolism, but only WDF downregulated the glycolysis pathway. Furthermore, the mechanical myocardial function was impaired in obese rats, being more relevant in WDF. In conclusion, both WD effectively triggered MetS features, although inflammation was detected just on the WDF-fed animals. Moreover, the WDF promoted a more pronounced functional, metabolic, and oxidative cardiac disorder, suggesting to be an adequate model for studying CVD in the scenario of MetS. Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Patology Botucatu Medical School São Paulo State University (UNESP) Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP) Department of Internal Medicine Botucatu Medical School São Paulo State University (UNESP) Department of Patology Botucatu Medical School São Paulo State University (UNESP) Department of Biostatistics Institute of Biosciences São Paulo State University (UNESP)

Obesity is considered an important risk factor for several disorders, such as diabetes mellitus, systemic arterial hypertension, dyslipidemia, and atherosclerosis, which are associated with inflammation and oxidative stress as a trigger factor. Passiflora edulis contains important bioactive compounds, such as phenolics, carotenoids, vitamin C, and polyamines in pulp, leaves, seeds, and bark. Aim: To evaluate the effect of bark of Passiflora edulis (BPe) on body composition, and metabolic and oxidative stress parameters in genetically obese mice. Methods: Obese male db/db mice (n = 14 animals) received normal feeds and water ad libitum for 8 weeks. Then, animals were randomly divided to continue either receiving standard chow (obese, n = 7 (OB)) or feed with standard chow plus bark Passiflora edulis (BPe) (obese + BPe, n = 7 (OB + BPe)) for 8 more weeks, totaling 16 weeks. BPe was added to chow (7 g of BPe/kg of chow corresponding to 1.5 g/kg of body weight). The parameters evaluated in animals included food and caloric intake, body weight, body fat, plasma glucose, triglycerides, and total cholesterol. Malondialdehyde and antioxidant capacity were evaluated in plasma and organs. Groups were compared by Student t-test, with p < 0.05. Results: BPe reduced visceral and subcutaneous fat deposit and adiposity index, cholesterol and triglyceride levels, ameliorated the antioxidant capacity, and reduced malondialdehyde (MDA) levels. Conclusion: the bark of Passiflora edulis was effective in improving body composition, and metabolic and antioxidant parameters in obese mice.

Made available in DSpace on 2022-04-29T08:27:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-01 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. Department of Internal Medicine Botucatu Medical School São Paulo State University Department of Pathology and Legal Medicine Ribeirão Preto Medical School University of São Paulo Department of Pathology Faculty of Medicine University of São Paulo Department of Internal Medicine Botucatu Medical School São Paulo State University