Navegando por Autor "Ferreira, Anderson José"

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Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart.
(2012) Gava, Elisandra; Castro, Carlos Henrique de; Ferreira, Anderson José; Colleta, Heloísa; Melo, Marcos Barrouin; Alenina, Natalia; Bader, Michael; Oliveira, Laser Antônio Machado de; Santos, Robson Augusto Souza dos
In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT2 on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and VI and fibronectin was performed using immunofluorescence-labeling and confocal microscopy. Picrosirius red staining was used for the histological assessment of the overall collagen distribution pattern. ECM proteins, metalloproteinases (MMP), ERK1/2 and p38 levels were quantified by western blot analysis. Gelatin zymography was used to evaluate the activity ofMMP-2 andMMP-9. We observed that the relative levels of collagen types I and III and fibronectin are significantly higher in both the right ventricle and AV valves of neonatal Mas−/− mouse hearts (e.g., collagen type I: 85.28±6.66 vs 43.50±4.41 arbitrary units in the right ventricles of Mas+/+ mice). Conversely, the level of collagen type VI was lower in the right ventricle and AV valves of Mas−/− mice. Adult Mas−/− mouse hearts presented similar patterns as observed in neonates. No significant differences in ECMprotein level were detected in atria. Likewise, no changes in ECM levels were observed in AT2 knockout mouse hearts. Although deletion of Mas induced a significant reduction in the level of the active form of MMP-2 in neonate hearts and a reduction of both MMP-2 and MMP-9 in adult Mas−/− mice, no significant differences were observed inMMP enzymatic activities when compared to controls. The levels of the active, phosphorylated forms of ERK1/2 and p38 were higher in hearts of both neonatal and adult Mas−/− mice. These observations suggest that Mas is involved in the selective expression of specific ECMproteins within both the ventricular myocardium and AV valves. The changes in the ECM profile may alter the connective tissue framework and contribute to the decreased cardiac performance observed in Mas−/− mice.
Antiarrhythmogenic effects of a neurotoxin from the spider Phoneutria nigriventer.
(2011) Almeida, Alvair Pinto de; Andrade, Alexandre Barbosa; Ferreira, Anderson José; Pires, Andrea Cristina Gomes; Damasceno, Dênis Derly; Alves, Márcia Netto Magalhães; Gomes, Enéas Ricardo de Morais; Kushmerick, Christopher; Lima, Ricardo de Freitas; Prado, Marco Antônio Maximo; Prado, Vânia Ferreira; Richardson, Michael; Cordeiro, Marta do Nascimento; Guatimosim, Silvia; Gomez, Marcus Vinicius
In this study, we evaluated the effects of PhKv, a 4584 Da peptide isolated from the spider Phoneutria nigriventer venom, in the isolated rat heart and in isolated ventricular myocytes. Ventricular arrhythmias were induced by occlusion of the left anterior descending coronary artery for 15 min followed by 30 min of reperfusion. Administration of native PhKv (240 nM) 1 min before or after reperfusion markedly reduced the duration of arrhythmias. This effect was blocked by atropine, thereby indicating the participation of muscarinic receptors in the antiarrhythmogenic effect of PhKv. Notably, recombinant PhKv (240 nM) was also efficient to attenuate the arrhythmias (3.8 0.9 vs. 8.0 1.2 arbitrary units in control group). Furthermore, PhKv induced a significant reduction in heart rate. This bradycardia was partially blunted by atropine and potentiated by pyridostigmine. To further evaluate the participation of acetylcholine on the PhKv effects, we examined the release of this neurotransmitter from neuromuscular junctions. It was found that Phkv (200 nM) significantly increased the release of acetylcholine in this preparation. Moreover, PhKv (250 nM) did not cause any significant change in action potential or Ca2þ transient parameters in isolated cardiomyocytes. Altogether, these findings show an important acetylcholine-mediated antiarrhythmogenic effect of the spider PhKv toxin in isolated hearts.
Bioactive glass containing 90% SiO2 in hard tissue engineering : an in vitro and in vivo characterization study.
(2019) Lehman, Luiz Felipe Cardoso; Noronha, Mariana Saturnino de; Diniz, Ivana Márcia Alves; Silva, Rosangela Maria Ferreira da Costa e; Andrade, Ângela Leão; Lima, Luiz Fernando de Sousa; Alcântara, Carlos Eduardo Pinto de; Domingues, Rosana Zacarias; Ferreira, Anderson José; Silva, Tarcília Aparecida da; Mesquita, Ricardo Alves de
Bioactive glass has been proved to have many applications in bioengineering due to its bone regenerative properties. In this work, an innovative, highly resorbable bioactive glass containing 90% SiO2 (BG90) to be used as a bone substitute was developed. The BG90 was synthetized by the sol–gel process with the dry step at room temperature. The biomaterial showed in vitro and in vivo bioactivities even with silica content up to 90%. Moreover, the BG90 presented high porosity and surface area due to its homogenously interconnected porous network. In vitro, it was observed to have high cell viability and marked osteoblastic differentiation of rat bone marrow‐derived cells when in contact with BG90 ion extracts. The BG90 transplantation into rat tibia defects was analysed at 1, 2, 3, 4, 7, and 10 weeks post‐operatively and compared with the defects of negative (no graft) and positive (autogenous bone graft) controls. After 4 weeks of grafting, the BG90 was totally resorbed and induced higher bone formation than did the positive control. Bone morphogenetic protein 2 (BMP‐2) expression at the grafting site peaked at 1 week and decreased similarly after 7 weeks for all groups. Only the BG90 group was still exhibiting BMP‐2 expression in the last experimental time. Our data demonstrated that the BG90 could be an attractive candidate to provide useful approaches in hard‐tissue bioengineering.
Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system.
(2013) Lautner, Roberto Queiroga; Villela, Daniel Campos; Silva, Rodrigo Araújo Fraga da; Silva, Neiva Caldeira; Braga, Thiago Verano; Fraga, Fabiana Costa; Jankowski, Joachim; Jankowski, Vera; Sousa, Frederico Barros de; Alzamora, Andréia Carvalho; Soares, Everton Rocha; Barbosa, Claudiane Maria; Kjeldsen, Frank; Oliveira, Aline Cristina; Braga, Janaina Félix; Savergnini, Silvia Silveira Quintão; Etelvino, Gisele Maia; Peluso, Antonio Augusto Bastos; Silva, Danielle Gomes Passos; Ferreira, Anderson José; Alves, Fabiana; Martins, Almir de Sousa; Raizada, Mohan K.; Paula, Renata Dutra de; Santos, Daisy Motta; Klempin, Friederike; Pimenta, Adriano Monteiro de Castro; Alenina, Natalia; Sinisterra Millán, Ruben Dario; Bader, Michael; Santos, Maria José Campagnole dos; Santos, Robson Augusto Souza dos
The renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.
Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.
(2010) Gomes, Aline Alves Lara; Damasceno, Dênis Derly; Pires, Rita Gomes Wanderley; Gros, Robert; Gomes, Enéas Ricardo de Morais; Gavioli, Mariana; Lima, Ricardo de Freitas; Guimarães, Diogo Aparecido da Silva; Lima, Patrícia Maria d'Almeida; Bueno Júnior, Carlos Roberto; Vasconcelos, Anilton Cesar; Campos, Danilo Roman; Menezes, Cristiane Alves da Silva; Sirvente, Raquel de Assis; Salemi, Vera Maria Cury; Mady, Charles; Caron, Marc G.; Ferreira, Anderson José; Brum, Patricia Chakur; Resende, Rodrigo Ribeiro; Cruz, Jader dos Santos; Gomez, Marcus Vinicius; Prado, Vânia Ferreira; Almeida, Alvair Pinto de; Prado, Marco Antônio Maximo; Fonseca, Silvia Carolina Guatimosim
Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.
Increased activity of the renin-angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low-protein diet.
(2013) Gomide, Joelma Maria Cardoso; Menezes, Rodrigo Cunha Alvim de; Fernandes, Luciano Gonçalves; Silva, Fernanda Cacilda dos Santos; Cardoso, Leonardo Máximo; Miranda, P. H.; Silva Junior, Luiz Gonzaga da; Lima, Mercia de Paula; Pesquero, Jorge Luiz; Heida, Giselle Foureaux; Ferreira, Anderson José; Chianca Júnior, Deoclécio Alves
Previous studies have shown that postweaning protein restriction induces changes in the sympathetic nervous system in rats, leading to alterations in cardiovascular parameters. In addition, the renin–angiotensin system is also affected in these animals. Here, we hypothesized that adjustments in the interaction between the RAS and SNS underlie the cardiovascular adaptations observed in rats fed a low-protein diet. Thus, we evaluated the alterations in the mean arterial pressure (MAP) and heart rate of Fisher rats fed a protein-deficient diet before and after systemic administration of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II (Ang II) type 1 (AT1) receptor antagonist losartan alone or in combination with the α1-adrenergic receptor antagonist prazosin. Administration of enalapril or losartan decreased the MAP only of rats under protein restriction. Prazosin injection after the infusion of losartan caused a further decrease in the MAP of malnourished rats. In contrast, only the administrationof prazosin elicited a reductionin theMAPof control animals.Whenthe sequence of administrationof the antagonistswasinverted, infusion of prazosin inanimals fedthe standard or the low-protein diet induced a reduction in the MAP that was further decreased by the subsequent injection of losartan. Importantly, in both protocols the responses ofmalnourished animals to losartan were markedly greater when compared with the control group. Moreover, these animals presented lower levels of circulatingAng II and a reduced responsiveness to Ang II. In contrast, the expression of AT1 receptors in the aorta ofmalnourished animals was increased. Thus, our data suggest that the renin–angiotensin system is an important factor supporting blood pressure in rats fed a low-protein diet and that the sympathetic nervous system activity in these animals is under strong influence of Ang II acting via AT1 receptors.
The angiotensin-(1-7)/Mas receptor axis is expressed in sinoatrial node cells of rats.
(2011) Ferreira, Anderson José; Moraes, Patrícia Lanza de; Foureaux, Giselle; Andrade, Alexandre Barbosa; Santos, Robson Augusto Souza dos; Almeida, Alvair Pinto de