ALFREDO INACIO FIORELLI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- 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.
- MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy(2014) FERREIRA, Ludmila Rodrigues Pinto; FRADE, Amanda Farage; SANTOS, Ronaldo Honorato Barros; TEIXEIRA, Priscila Camillo; BARON, Monique Andrade; NAVARRO, Isabela Cunha; BENVENUTI, Luiz Alberto; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; STOLF, Noedir Antonio; CHEVILLARD, Christophe; KALIL, Jorge; CUNHA-NETO, EdecioBackground/methods: Chagas disease is caused by an intracellular parasite, Trypanosoma cruzi, and it is a leading cause of heart failure in Latin America. The main clinical consequence of the infection is the development of a Chronic Chagas disease Cardiomyopathy (CCC), which is characterized by myocarditis, hypertrophy and fibrosis and affects about 30% of infected patients. CCC has a worse prognosis than other cardiomyopathies, like idiopathic dilated cardiomyopathy (DCM). It is well established that myocardial gene expression patterns are altered in CCC, but the molecular mechanisms underlying these differences are not clear. MicroRNAs are recently discovered regulators of gene expression, and are recognized as important factors in heart development and cardiovascular disorders (CD). We analyzed the expression of nine different miRNAs inmyocardial tissue samples of CCC patients in comparison to DCM patients and samples from heart transplant donors. Using the results of a cDNA microarray database on CCC and DCM myocardium, signaling networks were built and nodal molecules were identified. Results: We observed that five miRNAs were significantly altered in CCC and three in DCM; importantly, three miRNAs were significantly reduced in CCC as compared to DCM. We observed that multiple gene targets of the differentially expressed miRNAs showed a concordant inverse expression in CCC. Significantly, most gene targets and involved networks belong to crucial disease-related signaling pathways. Conclusion: These results suggest that miRNAs may play a major role in the regulation of gene expression in CCC pathogenesis, with potential implication as diagnostic and prognostic tools.
- Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas' disease reactivation after heart transplantation(2014) BENVENUTI, Luiz A.; ROGGERIO, Alessandra; NISHIYA, Anna S.; CAMPOS, Silvia V.; FIORELLI, Alfredo I.; LEVI, Jose E.BACKGROUND: Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. METHODS: The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. RESULTS: The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 x 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49 x 10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). CONCLUSIONS: Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx.
- Immunohistochemical Quantification of Inflammatory Cells in Endomyocardial Biopsy Fragments After Heart Transplantation: A New Potential Method to Improve the Diagnosis of Rejection After Heart Transplantation(2014) BOCCHI, E. A.; TANIGAWA, R. Y.; BRENDAO, S. M. G.; CRUZ, F.; ISSA, V.; AYUB-FERREIRA, S.; CHIZZOLA, P.; SOUZA, G.; FIORELLI, A. I.; BACAL, F.; POMERANTZEFF, P. M. A.; HONORATO, R.; LOURENCO-FILHO, D.; GUIMARAES, G.; BENVENUTI, L. A.Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P =.000). One patient with CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm(2) areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.
- Leukocyte Depletion During CPB: Effects on Inflammation and Lung Function(2014) AMORIM, Celio Gomes de; MALBOUISSON, Luiz Marcelo Sa; SILVA JR., Francisco Costa da; FIORELLI, Alfredo Inacio; MURAKAMI, Caroline Kameio Fernandes; CARMONA, Maria Jose CarvalhoCardiopulmonary bypass (CPB) is related to inflammatory response and pulmonary dysfunction. The aim of this study was to evaluate the effects of CPB leukocyte filtration on inflammation and lung function after coronary artery bypass grafting (CABG). A prospective randomized study was performed to compare CABG patients undergoing CPB leukocyte filtration (n = 9) or standard CPB (n = 11). Computed tomography, oxygenation, leukocyte count, hemodynamic data, PaO2/FiO(2), shunt fraction, interleukins, elastase, and myeloperoxidase were evaluated. Data were analyzed using two-factor ANOVA for repeated measurements. The filtered group showed lower neutrophil counts up to 50 min of CPB, lower shunt fraction up to 6 h after surgery, and lower levels of IL-10 at the end of surgery (p < 0.05). There was no statistically significant difference between groups related to other parameters. Leukodepletion during CPB results in neutrophil sequestration by a short time, decreased IL-10 serum levels, and lower worsening of lung function only temporarily.
- NHETS - Estudo de Necrópsias de Pacientes Submetidos a Transplante Cardíaco(2014) VALETTE, Thiago Ninck; AYUB-FERREIRA, Silvia Moreira; BENVENUTI, Luiz Alberto; ISSA, Victor Sarli; BACAL, Fernando; CHIZZOLA, Paulo Roberto; SOUZA, Germano Emilio Conceição; FIORELLI, Alfredo Inácio; SANTOS, Ronaldo Honorato Barros dos; BOCCHI, Edimar AlcidesBackground: Discrepancies between pre and post-mortem diagnoses are reported in the literature, ranging from 4.1 to 49.8 % in cases referred for necropsy, with important impact on patient treatment. Objective: To analyze patients who died after cardiac transplantation and to compare the pre- and post-mortem diagnoses. Methods: Perform a review of medical records and analyze clinical data, comorbidities, immunosuppression regimen, laboratory tests, clinical cause of death and cause of death at the necropsy. Then, the clinical and necroscopic causes of death of each patient were compared. Results: 48 deaths undergoing necropsy were analyzed during 2000-2010; 29 (60.4 %) had concordant clinical and necroscopic diagnoses, 16 (33.3%) had discordant diagnoses and three (6.3%) had unclear diagnoses. Among the discordant ones, 15 (31.3%) had possible impact on survival and one (2.1%) had no impact on survival. The main clinical misdiagnosis was infection, with five cases (26.7 % of discordant), followed by hyperacute rejection, with four cases (20 % of the discordant ones), and pulmonary thromboembolism, with three cases (13.3% of discordant ones). Conclusion: Discrepancies between clinical diagnosis and necroscopic findings are commonly found in cardiac transplantation. New strategies to improve clinical diagnosis should be made, considering the results of the necropsy, to improve the treatment of heart failure by heart transplantation.
conferenceObject THE TRANSPULMONARY GRADIENT BUT NOT THE SYSTOLIC OR MEAN PULMONARY ARTERIAL PRESSURE CORRELATES WITH THE WALL THICKNESS OF PERIPHERAL PULMONARY ARTERIES AND VEINS IN PATIENTS WITH CHRONIC HEART FAILURE(2014) AIELLO, Vera D.; CAMPOS, Pompeu R.; ISSA, Victor; HONORATO, Ronaldo; FIORELLI, Alfredo I.; BOCCHI, Edimar A.