Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina / Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

Influência do Consumo de Suco de Laranja (Citrus Sinensis) na Remodelação Cardíaca de Ratos Submetidos a Infarto do Miocárdio / Influence of Consumption of Orange Juice (Citrus Sinensis) on Cardiac Remodeling of Rats Submitted to Myocardial Infarction

Resumo Fundamento O suco de laranja (SL) é rico em polifenóis com propriedades anti-inflamatórias e antioxidantes. Após o infarto do miocárdio (IM), mudanças complexas ocorrem na estrutura e na função cardíacas, processo conhecido como remodelação cardíaca (RC). O estresse oxidativo e a inflamação podem modular esse processo. Nossa hipótese foi a de que o consumo de SL atenua a RC após o IM. Objetivos Avaliar a influência do SL sobre a RC após IM pela análise de variáveis funcionais, morfológicas, de estresse oxidativo, de inflação, e de metabolismo energético. Métodos Um total de 242 ratos machos pesando entre 200 e 250g foram submetidos a um procedimento cirúrgico (ligação da artéria coronária ou cirurgia simulada). Sete dia após a cirurgia, os animais sobreviventes foram divididos para um dos quatro grupos: 1) SM, animais sham que receberam água e maltodextrina (n= 20); 2) SSL, animais sham que receberam SL (n= 20); 3) IM, animais infartados que receberam água e maltodextrina (n= 40); e 4) ISL, animais infartados que receberam SL (n = 40). A análise estatística foi realizada pelo teste de ANOVA com dois fatores com o teste de Holm-Sidak. Os resultados foram apresentados em média ± desvio padrão, e o nível de significância adotado foi de 5%. Resultados Três meses depois, o IM levou à hipertrofia do ventrículo esquerdo (VE), com disfunção sistólica e diastólica, e aumento nos mediadores inflamatórios e de estresse oxidativo. Os animais que consumiram SL apresentaram menor atividade da glutationa peroxidase e maior expressão da heme-oxigenase-1 (HO-1). Conclusão O SL atenuou a RC, e a HO-1 pode exercer um importante papel nesse processo.

Abstract Background Orange juice (OJ) is rich in polyphenols with anti-inflammatory and antioxidant properties. After myocardial infarction (MI), complex changes occur in cardiac structure and function, which is known as cardiac remodeling (CR). Oxidative stress and inflammation can modulate this process. We hypothesized that the consumption of OJ attenuates the CR after MI. Objectives To evaluate the influence of OJ on CR after MI by analysis of functional, morphological, oxidative stress, inflammation, and energy metabolism variables. Methods A total of 242 male rats weighing 200-250 g were submitted to a surgical procedure (coronary artery ligation or simulated surgery). Seven days after surgery, survivors were assigned to one of the four groups 1) SM, sham animals with water and maltodextrin (n= 20); 2) SOJ, sham animals with OJ (n= 20); 3) IM, infarcted animals with water and maltodextrin (n= 40); and 4) IOJ, infarcted animals with OJ (n = 40). Statistical analysis was performed by the two-way ANOVA supplemented by Holm-Sidak. Results are presented as mean ± standard deviation, the level of significance adopted was 5%. Results After 3 months, MI led to left ventricular (LV) hypertrophy, with systolic and diastolic dysfunction, and increased oxidative stress and inflammatory mediators. OJ intake reduced LV cavity and improved systolic and diastolic function. The OJ animals presented lower activity of glutathione peroxidase and higher expression of heme-oxygenase-1 (HO-1). Conclusion OJ attenuated CR in infarcted rats and HO-1 may be play an important role in this process.

A Simple System to Predict Mortality in Medical Intensive Care Unit.

Background: Advances in critical care have increased survival chances and the demand for a scientific approach to outcome prediction. The present study aimed to investigate the associations of clinical information, demographic and laboratory data with mortality; and to elaborate and validate a regression equation for mortality prediction in a medical intensive care unit (ICU). Methods: This study included 202 patients and took place in a medical ICU at the Botucatu Medical School Hospital, Brazil. In Phase 1, 123 patients admitted to ICU between September 2003 and October 2004 was retrospectively analyzed and allowed equation elaboration. In Phase 2, the mortality equation was prospectively applied in 79 patients consecutively admitted to ICU between August and December 2006. Results: Among Phase 1 patients, 55% were males and mean age was 58±19 years. Mortality rate was 29%. Multivariate analysis revealed that shock (p=0.002) and hypoalbuminemia (p=0.024) were associated with higher mortality rate. When regression equation was applied in Phase 2 patients, higher equation values were shown for nonsurvivors (0.512; -1.008 -0.512) than for survivors (-1.008; -1.290 -1.008) (p=0.03). The equation also had good precision, 1.8% (IC95%; 1.1-4.7), and low bias, -3.1% (IC95%; -27.1 -20.8). Areas under the receiver operating characteristic (ROC) curve showed no statistical differences between APACHE II (0.75±0.06) and the equation (0.66±0.07) (p=0.27). Conclusions: Our data suggest that a simple and accurate prognostic equation can be used to predict ICU mortality.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats. .