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Role of inflammatory cytokines in cardiac remodeling in rats with Aortic Stenosis treated with dexamethasone


Heart failure (HF) is a complex syndrome that affects 23 million people worldwide. The heart of HF patients presents cardiac remodeling, cardiac dysfunction and some of the implications involved in cardiac remodeling are determined mainly by inflammation. Thus, we hypothesized that treatment with dexamethasone (DEX) may identify cytokines which could be used as therapeutic target for cardiac remodeling. Therefore, the objective of this study is to evaluate the effects of dexamethasone (DEX), a synthetic glucocorticoid with potent anti-inflammatory action, o hemodynamic, neural and inflammatory responses, and to identify possible therapeutic targets for cardiac remodeling in an experimental model of aortic stenosis. Therefore, 141 male wistar rats (80g) will be divided into two protocols. Protocol 1 / 132 rats will be divided into sham group ; dexamethasone-treated sham group, DEX; aortic stenosis (AS) and DEX-treated AS (AS+DEX). Protocol 2 / 9 rats will be treated with inhibitor of the target found in the protocol 1. All animals will be subjected to a maximum capacity test (TEM) test on a treadmill. HF groups will be anesthetized and submitted to aortic stenosis surgery and sham groups will undergo fictitious surgery. On the following day an echocardiographic analysis will be performed under anesthesia (0.5% -2% isoflurane mixture and 98% O2 in 1.5 L / min flow) and then 6 months days will be taken for HF progression. Animals will be treated with DEX for the last 15 days (50µg / kg, s.c.) or saline. At the end of the protocol, all animals will perform the last TEM and echocardiographic examination. Subsequently, under anesthesia, the animals will be catheterized (femoral artery) and, after 24 hours, blood pressure (BP) will be recorded for basal BP and autonomic nervous system activity analysis. In the end, the animals will be euthanized under anesthetic overload. The myocardium will be extracted for analysis of protein expression of inflammatory cytokines. Myocardium will also be used for morphometric analysis. The lung tissues will be removed and weighed. Results will be presented as mean ± standard error of the mean (SEM). For samples with normal distribution, parametric tests (One and Two Way-ANOVA) will be used. Samples with abnormal distribution will be automatically adjusted to meet normality standards by SigmaStat 3.0 software. Samples with significant differences will be analyzed by Tukey post-hoc (p <0.05). (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MIOTTO, DANYELLE SIQUEIRA; DUCHATSCH, FRANCINE; DIONIZIO, ALINE; BUZALAF, MARILIA AFONSO RABELO; AMARAL, SANDRA LIA. Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms. BIOMEDICINES, v. 11, n. 5, p. 17-pg., . (19/26117-8, 19/26070-1, 19/25603-6)
DE PAULA, VINICIUS F. F.; TARDELLI, LIDIELI P. P.; AMARAL, SANDRA L. L.. Dexamethasone-Induced Arterial Stiffening Is Attenuated by Training due to a Better Balance Between Aortic Collagen and Elastin Levels. CARDIOVASCULAR DRUGS AND THERAPY, v. N/A, p. 11-pg., . (17/00509-1, 19/25603-6)
MACEDO, ANDERSON G.; MIOTTO, DANYELLE S.; TARDELLI, LIDIELI P.; SANTOS, CARLOS F.; AMARAL, SANDRA L.. Exercise-induced angiogenesis is attenuated by captopril but maintained under perindopril treatment in hypertensive rats. FRONTIERS IN PHYSIOLOGY, v. 14, p. 13-pg., . (14/23229-6, 19/25603-6)

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