RONALDO HONORATO BARROS DOS SANTOS
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11
Projetos de Pesquisa
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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
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- Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy(2013) FRADE, Amanda Farage; TEIXEIRA, Priscila Camilo; IANNI, Barbara Maria; PISSETTI, Cristina Wide; SABA, Bruno; WANG, Lin Hui Tzu; KURAMOTO, Andreia; NOGUEIRA, Luciana Gabriel; BUCK, Paula; DIAS, Fabricio; GINIAUX, Helene; LLORED, Agnes; ALVES, Sthefanny; SCHMIDT, Andre; DONADI, Eduardo; MARIN-NETO, Jose Antonio; HIRATA, Mario; SAMPAIO, Marcelo; FRAGATA, Abilio; BOCCHI, Edimar Alcides; STOLF, Antonio Noedir; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato Barros; RODRIGUES, Virmondes; PEREIRA, Alexandre Costa; KALIL, Jorge; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheAims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.
conferenceObject A New Allocation System for Priorization in Heart Transplantation in the State of Sao Paulo - Brazil: Its Impact on Patients in ECMO(2022) STEFFEN, Samuel P.; GAIOTTO, Fabio A.; GASPAR, Shyrline F.; SANTOS, Ronaldo Honorato B.; FILHO, Domingos D. L.; BACAL, Fernando; JATENE, Fabio B.conferenceObject Reduction of right ventricle dysfunction and tricuspid regurgitation after bicaval orthotopic heart transplantation with HTK-Custodiol(2014) MANGINI, SSandrigo; GAIOTTO, F. A.; SANTOS, R. H. B.; FILHO, D. D. L.; MARCONDES-BRAGA, F. G.; POMERANTZEFF, P. M. A.; IMBERG, C.; KAWABE, L.; BACAL, F.; JATENE, F. B.- Frofile of Donor Hearts in Brazil(2014) MELO, J. L.; PAULO, A. R.; SOUZA, J. A.; OHE, L. A.; BARBOSA, M. B.; AVILA, M. S.; MARCONDES-BRAGA, E. G.; SEGURO, L. B.; MANGINI, S.; SANTOS, R. H.; LOURENCO FILHO, D. D.; GAIOTTO, F. A.; KAWABE, L. T.; BACAL, F.
- Diretriz de Assistência Circulatória Mecânica da Sociedade Brasileira de Cardiologia(2016) AYUB-FERREIRA, Silvia Moreira; SOUZA NETO, Joao David de; ALMEIDA, Dirceu Rodrigues; BISELLI, Bruno; AVILA, Monica Samuel; COLAFRANCESCHI, Alexandre Siciliano; STEFANELLO, Bianca; CARVALHO, Braulio Matias de; POLANCZYK, Carisi Anne; GALANTINI, Danilo Ribeiro; BOCCHI, Edimar Alcides; CHAMLIAN, Eduardo Gregorio; HOJAIJ, Elaine Marques; GAIOTTO, Fabio Antonio; PINTON, Fabio Augusto; JATENE, Fabio Biscegli; RAMIRES, Felix Jose Alvarez; ATIK, Fernando Antibas; FIGUEIRA, Fernando; BACAL, Fernando; GALAS, Filomena Regina Barbosa Gomes; BRITO, Flavio de Souza; CONCEICAO-SOUZA, Germano Emilio; RIBEIRO, Gustavo Calado de Aguiar; PINHEIRO JUNIOR, Jairo Alves; SOUZA, Januario Manoel de; ROSSI NETO, Joao Manoel; LIMA, Jose Lindemberg da Costa; MEJIA, Juan Cosquillo; FERNANDES, Juliana Rolim; BAUMWORCEL, Leonardo; MOURA, Lidia Ana Zytynski; HAJJAR, Ludhmila Abrahao; BECK-DA-SILVA, Luis; ROHDE, Luis Eduardo Paim; SEGURO, Luis Fernando Bernal da Costa; PINHEIRO, Mabel Leite; PARK, Marcelo; FERNANDES, Marcelo Ramalho; MONTERA, Marcelo Westerlund; ALVES, Marco Stephan Lofrano; WANDERLEY JUNIOR, Mauro Rogerio de Barros; HOSSNE, Nelson; FERNANDES, Paulo Manuel Pego; LEMOS, Pedro; SCHNEIDEWIND, Rafael Otto; UCHOA, Ricardo Barreira; HONORATO, Ronaldo; MANGINI, Sandrigo; FALCAO, Sandra Nivea dos Reis Saraiva; LOPES, Sergio Augusto Veiga; STRABELLI, Tania Mara Varejao; GUIMARAES, Tereza Cristina Felippe; CAMPANILI, Ticiane Carolina Goncalves Faustino; ISSA, Victor Sarli
- Self-reported versus actigraphy-assessed sleep duration in the ELSA-Brasil study: analysis of the short/long sleep duration reclassification(2022) SANTOS, Ronaldo B.; GIATTI, Soraya; AIELO, Aline N.; SILVA, Wagner A.; PARISE, Barbara K.; CUNHA, Lorenna F.; SOUZA, Silvana P.; ALENCAR, Airlane P.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; DRAGER, Luciano F.Purpose This study was aimed to determine the magnitude and predictors of self-reported short/long sleep duration (SDUR) reclassifications using objective measurements. Methods Adult participants from the ELSA-Brasil study performed self-reported SDUR, 7-day wrist actigraphy, and a portable sleep study. We explored two strategies of defining self-reported SDUR reclassification: (1) short and long SDUR defined by <6 and >= 8h, respectively; (2) reclassification using a large spectrum of SDUR categories (<5, 5-6, 7-8, 8-9, and >9 h). Results Data from 2036 participants were used in the final analysis (43% males; age: 49 +/- 8 years). Self-reported SDUR were poorly correlated (r=0.263) and presented a low agreement with actigraphy-based total sleep time. 58% of participants who self-reported short SDUR were reclassified into the reference (6-7.99 h) or long SDUR groups using actigraphy data. 88% of participants that self-reported long SDUR were reclassified into the reference and short SDUR. The variables independently associated with higher likelihood of self-reported short SDUR reclassification included insomnia (3.5-fold), female (2.5-fold), higher sleep efficiency (1.35-fold), lowest O-2 saturation (1.07-fold), higher wake after sleep onset (1.08-fold), and the higher number of awakening (1.05-fold). The presence of hypertension was associated with a 3.4-fold higher chance of self-reported long SDUR reclassification. Analysis of five self-reported SDUR categories revealed that the more extreme is the SDUR, the greater the self-reported SDUR reclassification. Conclusion In adults, we observed a significant rate of short/long SDUR reclassifications when comparing self-reported with objective data. These results underscore the need to reappraise subjective data use for future investigations addressing SDUR.
- Myocardial Gene Expression of T-bet, GATA-3, Ror-gamma t, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed T(H)1-Type Response(2014) NOGUEIRA, Luciana Gabriel; SANTOS, Ronaldo Honorato Barros; FIORELLI, Alfredo Inacio; MAIRENA, Eliane Conti; BENVENUTI, Luiz Alberto; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; KALIL, Jorge; CUNHA-NETO, EdecioBackground. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (T(H)1/T(H)2/T(H)17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-gamma and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by T(H)2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-beta and IL-10) were not upregulated in CCC myocardium. Expression of T(H)1-related genes such as T-bet, IFN-gamma, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local T(H)1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-gamma production in CCC myocardium, therefore fueling inflammation.
- Endomyocardial Biopsy after Heart Transplantation. When is Too Late?(2019) CEPEDA, L. M. Guerrero; MARCONDES-BRAGA, F. G.; COSTA, D. M.; MENDES, R. M.; DUARTE, S.; OLIVEIRA, J. C.; WOSNIACK, I.; SEGURO, L. F.; MANGINI, S.; GAIOTTO, F.; SANTOS, R. H.; AVILA, M. S.; BACAL, F.
- Sildenafil vs. Sodium Nitroprusside for the Pulmonary Hypertension Reversibility Test Before Cardiac Transplantation(2012) FREITAS JR., Aguinaldo Figueiredo; BACAL, Fernando; OLIVEIRA JUNIOR, Jose de Lima; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato; MOREIRA, Luiz Felipe Pinho; SILVA, Christiano Pereira; MANGINI, Sandrigo; TSUTSUI, Jeane Mike; BOCCHI, Edimar AlcidesBackground: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. Objective: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. Methods: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 mu g/kg/min) or SIL (100 mg, single dose). Results: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 +/- 2.08 vs. 8.11 +/- 1.81 cm/s, p = 0.002; SNP: 6.64 +/- 1.51 vs. 7.72 +/- 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. Conclusion: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation. (Arq Bras Cardiol 2012;99(3):848-856)
- Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy(2011) TEIXEIRA, Priscila Camillo; SANTOS, Ronaldo Honorato Barros; FIORELLI, Alfredo Inacio; BILATE, Angelina Morand Bianchi; BENVENUTI, Luiz Alberto; STOLF, Noedir Antonio; KALIL, Jorge; CUNHA-NETO, EdecioBackground: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. Methodology/Principal Findings: Myocardium homogenates from CCC (N = 5), IC (N = 5) and IDC (N = 5) patients, as well as from heart donors (N = 5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. Conclusions/Significance: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.