EDECIO CUNHA NETO

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Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder

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Assunto: Cardiac & Cardiovascular Systems ×

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Agora exibindo 1 - 10 de 22
  • article 2 Citação(ões) na Scopus
    4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification
    (2023) KIYUNA, Ligia A.; CANDIDO, Darlan S.; BECHARA, Luiz R. G.; JESUS, Itamar C. G.; RAMALHO, Lisley S.; KRUM, Barbara; ALBUQUERQUE, Ruda P.; CAMPOS, Juliane C.; BOZI, Luiz H. M.; ZAMBELLI, Vanessa O.; ALVES, Ariane N.; CAMPOLO, Nicolas; MASTROGIOVANNI, Mauricio; BARTESAGHI, Silvina; LEYVA, Alejandro; DURAN, Rosario; RADI, Rafael; ARANTES, Guilherme M.; CUNHA-NETO, Edecio; MORI, Marcelo A.; CHEN, Che-Hong; YANG, Wenjin; MOCHLY-ROSEN, Daria; MACRAE, Ian J.; FERREIRA, Ludmila R. P.; FERREIRA, Julio C. B.
    Background and Aims Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.Methods Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets.Results 4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure.Conclusions 4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure. Structured Graphical Abstract The vicious cycle of heart failure (HF). (i) Impaired aldehyde metabolism by aldehyde dehydrogenase 2 (ALDH2); (ii) accumulation of 4-hydroxynonenal (4-HNE), a reactive aldehyde by-product of mitochondrial dysfunction; (iii) direct 4-HNE inhibition of Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis; and (iv) overall impairment of miRNA biogenesis, which negatively impacts HF outcome. Blue and red arrows/inhibitors represent the vicious cycle of HF and the benefits of small molecule activators of ALDH2 in HF, respectively.
  • conferenceObject
    Benznidazole treatment is associated with Trypanosoma cruzi blood PCR negativity and less cardiac lesions in Chagas disease: NIH SaMitrop Study
    (2017) CARDOSO, C. S.; SABINO, E. C.; OLIVEIRA, C. D. L.; OLIVEIRA, L. C.; FERREIRA, A. M.; BIERRENBACH, A. L.; SILVA, J. L. P.; COLOSIMO, E. A.; CUNHA-NETO, E.; RIBEIRO, A. L. P.
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    Plasma Biomarkers Reflecting High Oxidative Stress Predicts Myocardial Injury Related to Anthracycline Chemotherapy in the CECCY Trial
    (2018) WANDERLEY JR., Mauro R.; AVILA, Monica S.; FERNANDES-SILVA, Miguel M.; CUNHA-NETO, Edecio; CRUZ, Fatima D.; BRANDAO, Goncalves Sara M.; RIGAUD, Vagner O.; HAJJAR, Ludhmila A.; KALIL FILHO, Roberto; BOCCHI, Edimar A.; AYUB-FERREIRA, Silvia M.
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    Circulating miR-1 And miR-133b Correlate With Subclinical Myocardial Injury In Breast Cancer Patients Under Doxorubicin Treatment
    (2015) OLIVEIRA-CARVALHO, Vagner; FERREIRA, Ludmila R.; BORGES, Danielle P.; AYUB-FERREIRA, Silvia M.; AVILA, Monica S.; BRANDAO, Sara M.; CRUZ, Fatima; CUNHA-NETO, Edecio; BOCCHI, Edimar A.
  • article 11 Citação(ões) na Scopus
    SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease-2023
    (2023) MARIN-NETO, Jose Antonio; JR, Anis Rassi; OLIVEIRA, Glaucia Maria Moraes; CORREIA, Luis Claudio Lemos; RAMOS JUNIOR, Alberto Novaes; LUQUETTI, Alejandro Ostermayer; HASSLOCHER-MORENA, Alejandro Marcel; SOUSA, Andrea Silvestre de; PAOLA, Angelo Amato Vincenzo de; SOUSA, Antonio Carlos Sobral; RIBEIRO, Antonio Luiz Pinho; CORREIA FILHO, Dalmo; SOUZA, Dilma do Socorro Moraes de; CUNHA-NETO, Edecio; RAMIRES, Felix Jose Alvarez; BACAL, Fernando; NUNES, Maria do Carmo Pereira; MARTINELLI FILHO, Martino; SCANAVACCA, Maurici Ibrahim; SARAIVA, Roberto Magalhaes; OLIVEIRA JUNIOR, Wilson Alves de; LORGA-FILHO, Adalberto Menezes; GUIMARAES, Adriana de Jesus Benevides de Almeida; BRAGA, Adriana Lopes Latado; OLIVEIRA, Adriana Sarmento de; SARABANDA, Alvaro Valentim Lima; PINTO, Ana Yece das Neves; CARMO, Andre Assis Lopes do; SCHMIDT, Andre; COSTA, Andrea Rodrigues da; IANNI, Barbara Maria; MARKMAN FILHO, Brivaldo; ROCHITT, Carlos Eduardo; MACEDO, Carolina The; MADY, Charles; CHEVILLARD, Christophe; VIRGENS, Claudio Marcelo Bittencourt das; CASTRO, Cleudson Nery de; BRITTO, Constanca Felicia De Paoli de Carvalho; PISANI, Cristiano; RASSI, Daniel do Carmo; SOBRAL FILHO, Dario Celestino; ALMEIDA, Dirceu Rodrigues de; BOCCHI, Edimar Alcides; MESQUITA, Evandro Tinoco; MENDES, Fernanda de Souza Nogueira Sardinha; GONDIM, Francisca Tatiana Pereira; SILVA, Gilberto Marcelo Sperandio da; PEIXOTO, Giselle de Lima; LIMA, Gustavo Glotz de; VELOSO, Henrique Horta; MOREIRA, Henrique Turin; LOPES, Hugo Bellotti; PINTO, Ibraim Masciarelli Francisco; FERREIRA, Joao Marcos Bemfica Barbosa; NUNES, Joao Paulo Silva; BARRETO-FILHO, Jose Augusto Soares; SARAIVA, Jose Francisco Kerr; LANNES-VIEIRA, Joseli; OLIVEIRA, Joselina Luzia Menezes; ARMAGANIJAN, Luciana Vidal; MARTINS, Luiz Claudio; SANGENIS, Luiz Henrique Conde; BARBOSA, Marco Paulo Tomaz; ALMEIDA-SANTOS, Marcos Antonio; SIMOES, Marcos Vinicius; YASUDA, Maria Aparecida Shikanai; MOREIRA, Maria da Consolacao Vieira; HIGUCHI, Maria de Lourdes; MONTEIRO, Maria Rita de Cassia Costa; MEDIANO, Mauro Felippe Felix; LIMA, Mayara Maia; OLIVEIRA, Maykon Tavares de; ROMANO, Minna Moreira Dias; ARAUJO, Nadjar Nitz Silva Lociks de; MEDEIROS, Paulo de Tarso Jorge; ALVES, Renato Vieira; TEIXEIRA, Ricardo Alkmim; PEDROSA, Roberto Coury; ARAS JUNIOR, Roque; TORRES, Rosalia Morais; POVOA, Rui Manoel dos Santos; RASSI, Sergio Gabriel; ALVES, Silvia Marinho Martins; TAVARES, Suelene Brito do Nascimento; PALMEIRA, Swamy Lima; SILVA JUNIOR, Telemaco Luiz da; RODRIGUES, Thiago da Rocha; MADRINI JUNIOR, Vagner; BRANT, Veruska Maia da Costa; DUTRA, Walderez Ornelas; DIAS, Joao Carlos Pinto
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    Myocardial perfusion disturbance precedes LV systolic dysfunction in experimental model of chronic Chagas cardiomyopathy
    (2018) OLIVEIRA, L. F. L.; THACKERAY, J. T.; TANAKA, D. M.; MARIN-NETO, J. A.; ROMANO, M. M. D.; LOPES, C. D.; BARROS-FILHO, A. C. L.; RIBEIRO, F. F. F.; MEJIA, J.; MALAMUT, C.; BENGEL, F. M.; CUNHA-NETO, E.; HIGUCHI, M. L.; NEKOLLA, S. G.; SIMOES, M. V.
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    Endothelial inflammatory activation is related to myocardial perfusion disturbance in experimental chronic Chagas disease
    (2022) TANAKA, D. M.; FABRICIO, C. G.; MARIN-NETO, J. A.; BARROS-FILHO, A. C. L.; LOPES, C. D.; OLIVEIRA, L. F. L.; MEJIA, J.; ALMEIDA, R. R.; BATAH, S. S.; NEKOLLA, S. G.; HIGUCHI, M. L.; CUNHA-NETO, E.; FABRO, A. T.; ROMANO, M. M.; SIMOES, M. V.
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    Rest myocardial perfusion disturbance is related to inflammation but not to fibrosis inexperimental chronic chagas cardiomyopathy
    (2013) OLIVEIRA, L. F. L.; CARVALHO, E. E. V.; MEJIA, J.; SANTANA-SILVA, J.; ROMANNO, M. M. D.; CUNHA-NETO, E.; HIGUCHI, M. L.; MACIEL, B. C.; MARIN-NETO, J. A.; SIMOES, M. V.
  • article 1 Citação(ões) na Scopus
    Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats
    (2023) SOUSA, Marcelo Nunes de; ANUNCIACAO, Lucas Ferreira da; FREITAS, Pedro Luiz Zonta de; RICARDO-DA-SILVA, Fernanda Yamamoto; MOREIRA, Luiz Felipe Pinho; CORREIA, Cristiano Jesus; BREITHAUPT-FALOPPA, Ana Cristina
    OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17 beta-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17 beta-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17 beta-oestradiol (280 mg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1 beta, IL-10 and tumour necrosis factor-a were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17 beta-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17 beta-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1 beta increased after I/R and 17 beta-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1 beta and IL-10 in lung explants, reduced by 17 beta-oestradiol. CONCLUSIONS: Our results showed that 17 beta-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17 beta-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.
  • conferenceObject
    Pentoxifylline Reduces Inflammation And Myocardial Perfusion Derangements In Experimental Chronic Chagas Cardiomyopathy In Hamsters.
    (2022) TANAKA, Denise Mayumi; FABRICIO, Camila G.; MARIN-NETO, Jose A.; BARROS-FILHO, Antonio C. L.; LOPES, Carla D.; OLIVEIRA, Luciano F. L.; RESENDE, Alessandra A.; MOREIRA, Henrique T.; MEJIA, Jorge; HIGUCHI, Maria L.; CUNHA-NETO, Edecio; ROMANO, Minna M. D.; SCHMIDT, Andr E.; SIMOES, Marcus