Gender can influence post-infarction cardiac remodeling.
To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI).
...Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium.
MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI.
Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.
Abstract Background Since the cell therapy benefits for myocardial infarction are mainly related to infarct reduction by regenerating lost myocardium or increasing survival of tissues at risk, we ...evaluated the effects of bone marrow-derived mononuclear cells (MNC), implanted after the completion of necrosis, on infarct progression and cardiac remodeling. Methods After 48 h of induction of myocardial infarction (MI), Lewis-inbred rats were injected with 6 × 106 cells (MI + MNC) or saline (MI). After six weeks, scar dimension, ventricular morphology and function were analyzed by echocardiography followed by histomorphology of the infarcted and border zones. Results After therapy, the relative size of the infarct was smaller in MI + MNC (37 ± 1% of the left ventricle) than in MI (43 ± 1%). While the MI group exhibited parallel elongation of the infarcted (31.6 ± 3.8% increase) and reminiscent ventricular portions (33.5 ± 3.7%), MNC therapy preserved the initial infarct length. Infarcted walls were thicker (979 ± 31 mm) in the MNC group than in the untreated group (709 ± 41 mm), also demonstrating an absence of infarct expansion. In the border zones, MNC led to increased capillary densities and capillary/myocyte ratios. The cardiac systolic function remained depressed in MI, but improved by 19 ± 5% in MI + MNC which reduced the incidence of pulmonary arterial hypertension (37.5% in MI and 6.25% in MI + MNC). Conclusion MNC therapy prevented the infarct expansion and thinning related to cardiac remodeling and was associated with an improvement of border zone microcirculation: as a result, MNC therapy reduced typical MI dysfunctional repercussions.
This study evaluated modulators of apoptosis in the myocardium of rats subjected to exercise training. Rats were assigned to non-trained and exercise-trained groups, respectively. The animals ran for ...1 h per day, 6 times per week and, for a total of 13 weeks. The left ventricle was processed for analysis of gene and protein anti- (Bcl-2, c-IAP1, c-IAP2, Survivin, ILK, Akt and pAkt) and pro- (Bad) apoptotic expression by real-time PCR (except for Akt and pAkt) and Western blot, respectively. The Bad mRNA (p<0.05), but not the protein expression (p = 0.19), was significantly lower after training. The exercise training significantly increased the gene and protein expression for all anti-apoptotic factors. However, a significant change in the c-IAP2 was seen only for gene expression (p<0.05). The present findings indicate that exercise can create a favorable milieu for the survival of cardiomyocytes when apoptosis is increased.
El estudio analizó moduladores de la apoptosis en el miocardio de ratas entrenadas físicamente. Las ratas se dividieron en no entrenado y entrenadas. Los animales se ha ejecutado (60 por día x 6 semanas) a las 13 semanas. El ventrículo izquierdo se procesan para el análisis de la expresión de sus genes y proteínas que inhiben (Bcl-2, c-IAP1, c-IAP2, survivina, ILK, Akt y pAkt) y causa (Bad) de la apoptosis por PCR en tiempo real (excepto Akt y pAkt) y Western blot. El nivel de ARNm de Bad (p<0,05) se redujo después de la entrenamiento, pero no era diferente de proteína. La expresión de los inhibidores de la apoptosis fue significativamente mayor con la entrenamiento. La excepción fue para c-IAP2, que aumentó sólo en el nivel transcripcional (p<0,05). Los resultados de este estudio indican que el ejercicio crea un entorno buen para la supervivencia de la apoptosis de los cardiomiocitos.
Este estudo analisou moduladores de apoptose no miocárdio de ratos submetidos a treinamento físico. Os ratos foram distribuídos nos seguintes grupos, respectivamente: não treinados; treinados. Os animais realizaram exercício em esteira (60 min./dia; 6 x semana) por 13 semanas. O ventrículo esquerdo foi processado para análise da expressão gênica e protéica de fatores anti-apoptóticos (Bcl-2, c-IAP1, c-IAP2, Survivina, ILK, Akt e pAkt) e pro-apoptóticos (Bad) por PCR em tempo real (exceto Akt e pAkt) e Western blot, respectivamente. O teor de RNAm da Bad (p<0,05) foi significativamente reduzido após treinamento. Porém, a expressão protéica da Bad não foi diferente entre os grupos. A expressão gênica e proteica de todos os fatores anti-apoptóticos foi significativamente aumentada com o treinamento. A exceção foi para c-IAP2, que aumentou somente em nível transcripcional (p<0,05). Os achados deste estudo indicam que o exercício cria um ambiente favorável para sobrevivência dos cardiomiócitos a apoptose.
Exercise training effects on the contractility of aged myocardium have been investigated for more than 20 years, but the data are still unclear. This study evaluated the hypothesis that a swimming ...training (ST) may improve myocardial inotropism in older rats. Male Wistar rats aged 4 (young)-and 21 (old)-months-old were divided into young untrained (YNT), old untrained (ONT), and old trained (OTR; 6 weeks of ST) groups. Echocardiography and hemodynamic were employed to assess left ventricular morphology and function. Myocardial mechanics was evaluated on papillary muscles. Histological and immunoblotting were carried out to evaluate fibrosis and proteins that modulate the myocardial function and calcium handling. We found that older rats did not show cardiac dysfunction, but ONT group showed lower physical performance during a swimming test (YNT: 5 ± 2; ONT: -16 ± 0.4; OTR: 51 ± 3; Δ%, sec). Moreover, ONT group showed worse myocardial inotropism, in which it was reversed by ST (Peak developed tension: YNT: 6.2 ± 0.7; ONT: 3.9 ± 0.3; OTR: 6.9 ± 0.9; g/mm2). The ST was associated with preserved collagen content (YNT: 0.38 ± 0.05; ONT: 0.78 ± 0.12; OTR: 0.34 ± 0.09; %). Exercise partially mitigated the effects of aging on intracellular Ca2+-regulating protein (eg, L-Ca2+ channel and phospholamban) and β-isoform of myosin. Thus, we propose that these molecular alterations together with inhibition of collagen increase contribute to improved myocardial performance in older rats.
There was no data for cardiac repercussion of exercise training associated with tobacco smoking. This issue is interesting because some smoking people can be enrolled in an exercise-training program. ...Thus, we evaluated swimming training effects on the function and structural myocardial in rats exposed to tobacco smoking.
Male Wistar rats were assigned to one of four groups: C, untrained rats without exposure to tobacco smoking; E, exercised rats without exposure to tobacco smoking; CS, untrained rats exposed to tobacco smoking; ECS, exercised rats exposed to tobacco smoking. Rats swam five times a week twice daily (60min per session) for 8 weeks. Before each bout exercise, rats breathed smoke from 20 cigarettes for 60min. Twenty-four hours after the last day of the protocol, papillary muscles were isolated for in vitro analysis of myocardial mechanics. The myocardial mass and nuclear cardiomyocyte volume were used as hypertrophy markers, and collagen content was determined by picrosirius red staining.
There was a well-pronounced myocardial hypertrophic effect for two interventions. The exercise blunted myocardial collagen increases induced by tobacco smoking. However, exercise and tobacco-smoking association was deleterious to myocardial performance. Thereby, in vitro experiments with papillary muscles contracting in isometric showed impairment myocardial inotropism in exercised rats exposed to tobacco smoking.
This work presents novel findings on the role of exercise training on cardiac remodeling induced by tobacco smoking. Although exercise has mitigated tissue fibrosis, their association with tobacco smoking exacerbated hypertrophy and in vitro myocardial dysfunction.
This is first study to show that the association of an aerobic exercise training with tobacco smoking intensifies the phenotype of pathological cardiac hypertrophy. Therefore, the combination of interventions resulted in exacerbated myocardial hypertrophy and contractility dysfunction. These findings have significant clinical implication because some smoking people can be enrolled in an exercise-training program.
This study evaluated the effects of light-emitting diode (LED) on mesenchymal stem cells (MSCs). An electronic search was conducted in PubMed/MEDLINE, Scopus, and Web of Science database for articles ...published from 1980 to February 2020. Ten articles met the search criteria and were included in this review. The risk of bias was evaluated to report quality, safety, and environmental standards. MSCs were derived from adipose tissue, bone marrow, dental pulp, gingiva, and umbilical cord. Protocols for cellular irradiation used red and blue light spectrum with variations of the parameters. The LED has been shown to induce greater cellular viability, proliferation, differentiation, and secretion of growth factors. The set of information available leads to proposing a complex signaling cascade for the action of photobiomodulation, including angiogenic factors, singlet oxygen, mitogen-activated protein kinase/extracellular signal-regulated protein kinase, Janus kinase/signal transducer, and reactive oxygen species. In conclusion, although our results suggest that LED can boost MSCs, a nonuniformity in the experimental protocol, bias, and the limited number of studies reduces the power of systematic review. Further research is essential to find the optimal LED irradiation parameters to boost MSCs function and evaluate its impact in the clinical setting.
Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all ...patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks.
Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt
activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling-ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance.
Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility.
Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in ...the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with upregulation of the apical proximal tubule endocytic receptor megalin and of the podocyte main slit diaphragm proteins nephrin and podocin. Collectively, these findings demonstrate that DPPIV inhibition exerts renoprotective effects and ameliorates cardiorenal function in rats with established HF. Long-term studies with DPPIV inhibitors are needed to ascertain whether these effects ultimately translate into improved clinical outcomes.
OBJETIVO: Avaliar o nível de atividade física em professores da rede pública estadual de ensino. MÉTODOS: Estudo transversal conduzido com 1.681 professores de São Paulo, SP, em 2009. A versão curta ...do Questionário Internacional de Atividade Física foi aplicada e o nível de atividade física dos professores foi categorizado em baixo, moderado ou alto. A amostra foi estratificada por idade, região da cidade e sexo. O teste de qui-quadrado foi aplicado nas comparações e o nível de significância adotado foi de p < 0,05. RESULTADOS: A prevalência de nível baixo de atividade física foi de 46,3%, e os níveis moderado e alto representaram 42,7% e 11%, respectivamente. Níveis baixos de atividade física foram mais prevalentes em indivíduos de 31 a 42 anos (19,5%) e menor prevalência foi observada de 55 a 66 anos (5,7%). Níveis moderados e altos foram menos prevalentes em idade mais avançada. Mais professores apresentaram nível baixo (50,5%) e alto (11,4%) de atividade física na região leste em relação à sul (baixo: 48,6%; alto: 8.1%). O número de professores com nível moderado foi significativamente menor na região leste (38,1%) comparada à sul (43,3%). O número de homens com nível baixo (53%) e alto (14,1%) de atividade física foi significantemente maior que em mulheres (baixo: 42,9%; alto: 9,4%). A prevalência de homens com nível moderado (32,9%) foi significativamente menor em comparação às mulheres (47,7%). CONCLUSÕES: A prevalência de nível baixo de atividade física foi marcadamente elevada. Diferenças nas idades, regiões e sexos devem ser consideradas no planejamento e direcionamento de campanhas que visem promover aumento dos níveis de atividade física nessa população.
OBJECTIVE: To assess the level of physical activity in public school teachers. METHODS: Cross-sectional study conducted with 1,681 teachers from the city of São Paulo, southeastern Brazil, in 2009. The International Physical Activity Questionnaire short version was applied and the level of physical activity was categorized as low, moderate or high. The study sample was stratified by age, gender and area of the city (south and east). The chi-square test was used for comparisons at a 5% level of significance. RESULTS: The prevalence of low, moderate and high levels of physical activity was 46.3%, 42.7% and 11%, respectively. Low physical activity was more prevalent among those aged 31 to 42 years (19.5%) and less prevalent among those aged 55 to 66 (5.7%). Moderate and high levels of physical activity were less prevalent among older teachers. A greater proportion of teachers showed low and high levels of physical activity in the east compared to the south of the city (50.5% vs. 48.6%; 11.4% vs. 8.1%, respectively). The proportion of teachers reporting moderate physical activity was significantly lower in the east (38.1%) compared to the south of the city (43.3%). Low and high levels of physical activity were significantly higher in men than women (53% vs. 42.9%; 14.1% vs. 9.4%, respectively). The prevalence of moderate level of physical activity was significantly lower in men (32.9%) than women (47.7%). CONCLUSIONS: The prevalence of low physical activity was strikingly high. Variables such as age, gender and city area should be taken into account while planning and targeting campaigns aimed at promoting increased physical activity in this population.
OBJETIVO: Evaluar el nivel de actividad física en profesores de la red pública estatal de educación. MÉTODOS: Estudio transversal conducido con 1.681 profesores de Sao Paulo, sureste de Brasil, en 2009. La versión corta del Cuestionario Internacional de Actividad Física fue aplicada y el nivel de actividad física de los profesores fue categorizado en bajo, moderado o alto. La muestra fue estratificada por edad, región de la ciudad y sexo. La prueba de chi-cuadrado fue aplicada en las comparaciones y el nivel de significancia adoptado fue de p<0,05. RESULTADOS: La prevalencia de nivel bajo de actividad física fue de 46,3%, y los niveles moderado y alto representaron 42,7% y 11%, respectivamente. Niveles bajos de actividad física fueron más prevalecientes en individuos de 31 a 42 años (19,5%) y menor prevalencia fue observada de 55 a 66 años (5,7%). Niveles moderados y altos fueron menos prevalecientes en edad más avanzada. Un mayor número de profesores presentó nivel bajo (50,5%) y alto (11,4%) de actividad física en la región este con relación a la sur (bajo: 48,6%; alto: 8,1%). El número de profesores con nivel moderado fue significativamente menor en la región este (38,1%) comparada con la región sur (43,3%). El número de hombres con nivel bajo (53%) y alto (14,1%) de actividad física fue significativamente mayor que el de las mujeres (bajo: 42,9%); alto: 9,4%). La prevalencia de hombres con nivel moderado (32,9%) fue significativamente menor en comparación con el de las mujeres (47,7%). CONCLUSIONES: La prevalencia de nivel bajo de actividad física fue marcadamente elevada. Diferencias en las edades, regiones y sexos deben ser consideradas en la planificación y direccionamiento de campañas que apuntan promover aumento de los niveles de actividad física en esta población.