GABRIELA VENTURINI DA SILVA

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LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: ALEXANDRE DA COSTA PEREIRA ×

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Agora exibindo 1 - 10 de 27
  • article 2 Citação(ões) na Scopus
    Different Transcriptomic Response to T. cruzi Infection in hiPSC-Derived Cardiomyocytes From Chagas Disease Patients With and Without Chronic Cardiomyopathy
    (2022) OLIVEIRA, Theo G. M.; VENTURINI, Gabriela; ALVIM, Juliana M.; FEIJO, Larissa L.; DINARDO, Carla L.; SABINO, Ester C.; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.
    Chagas disease is a tropical zoonosis caused by Trypanosoma cruzi. After infection, the host present an acute phase, usually asymptomatic, in which an extensive parasite proliferation and intense innate immune activity occurs, followed by a chronic phase, characterized by low parasitemia and development of specific immunity. Most individuals in the chronic phase remain without symptoms or organ damage, a state called indeterminate IND form. However, 20 to 40% of individuals develop cardiac or gastrointestinal complications at any time in life. Cardiomyocytes have an important role in the development of Chronic Chagas Cardiomyopathy (CCC) due to transcriptional and metabolic alterations that are crucial for the parasite survival and replication. However, it still not clear why some infected individuals progress to a cardiomyopathy phase, while others remain asymptomatic. In this work, we used hiPSCs-derived cardiomyocytes (hiPSC-CM) to investigate patterns of infection, proliferation and transcriptional response in IND and CCC patients. Our data show that T. cruzi infection and proliferation efficiency do not differ significantly in PBMCs and hiPSC-CM from both groups. However, RNA-seq analysis in hiPSC-CM infected for 24 hours showed a significantly different transcriptional response to the parasite in cells from IND or CCC patients. Cardiomyocytes from IND showed significant differences in the expression of genes related to antigen processing and presentation, as well as, immune co-stimulatory molecules. Furthermore, the downregulation of collagen production genes and extracellular matrix components was significantly different in these cells. Cardiomyocytes from CCC, in turn, showed increased expression of mTORC1 pathway and unfolded protein response genes, both associated to increased intracellular ROS production. These data point to a differential pattern of response, determined by baseline genetic differences between groups, which may have an impact on the development of a chronic outcome with or without the presentation of cardiac symptoms.
  • article 7 Citação(ões) na Scopus
    Obstructive sleep apnoea is associated with myocardial injury in patients with refractory angina
    (2016) GEOVANINI, Glaucylara R.; PEREIRA, Alexandre C.; GOWDAK, Luis H. W.; DOURADO, Luciana Oliveira Cascaes; POPPI, Nilson T.; VENTURINI, Gabriela; DRAGER, Luciano F.; LORENZI-FILHO, Geraldo
    Objective To investigate the association between obstructive sleep apnoea (OSA) severity with markers of overnight myocardial injury in patients with refractory angina. Methods Patients with refractory angina were characterised clinically and they underwent ischaemia imaging stress tests by single-photon emission computed tomography (SPECT) and/or cardiac MRI. The patients were admitted to the hospital, remained under resting conditions for blood determination of high-sensitivity cardiac troponin T (hs-cTnT) at 14:00, 22:00 and after overnight polysomnography at 7:00. Results We studied 80 consecutive patients (age: 62 +/- 10 years; male: 66%; body mass index (BMI): 29.5 +/- 4 kg/m(2)) with well-established diagnosis of refractory angina. The mean apnoea-hypopnoea index (AHI) was 37 +/- 29 events/h and OSA (AHI >15 events/h) was present in 75% of the population. Morning detectable hs-cTnT and above 99th percentile was present in 88% and 36% of the population, respectively. Patients in the first to third quartiles of OSA severity did not have circadian variation of hs-cTnT. In contrast, patients in the fourth quartile (AHI >= 51 events/h) had a circadian variation of hs-cTnT with a morning peak of hs-cTnT that was two times higher than that in the remaining population (p = 0.02). The highest quartile of OSA severity remained associated with the highest quartile of hs-cTnT (p = 0.028) in multivariate analysis. Conclusion Very severe OSA is common and independently associated with overnight myocardial injury in patients with refractory angina.
  • conferenceObject
    Trypanosoma cruzi cardiomyocyte infection promotes innate immune response and metabolic rewiring
    (2022) VENTURINI, Gabriela; ALVIM, Juliana; PADILHA, Kallyandra; TOEPFER, Christopher; GORHAM, Joshua; BIAGI, Diogo; SCHENKMAN, Sergio; CARVALHO, Valdemir; SALGUEIRO, Jessica; CARDOZO, Karina; KRIEGER, Jose; PEREIRA, Alexandre; SEIDMAN, Jonathan; SEIDMAN, Christine
  • conferenceObject
    Correlation betwen the metabolome and binder of ST2 receptor in chronic periodontics in elderly
    (2016) BORGES, A.; CARVALHO, M.; VENTURINI, G.; VIEIRA, C.; PAULINO, T.; MIGUEL, C. Botelho; OLIVEIRA, C.; PEREIRA, A.; BINVIGNAT, O.; RODRIGUES, W.
  • article 2 Citação(ões) na Scopus
    Loss of mTORC2 Activity in Neutrophils Impairs Fusion of Granules and Affects Cellular Metabolism Favoring Increased Bacterial Burden in Sepsis
    (2021) BREDA, Cristiane Naffah de Souza; BREDA, Leandro Carvalho Dantas; CARVALHO, Larissa Anastacio da Costa; AMANO, Mariane Tami; TERRA, Fernanda Fernandes; SILVA, Reinaldo Correia; FRAGAS, Matheus Garcia; FORNI, Maria Fernanda; FONSECA, Monique Thais Costa; VENTURINI, Gabriela; FEITOSA, Amanda Campelo Melo; GHIROTTO, Bruno; CRUZ, Mario Costa; CUNHA, Flavia Franco; IGNACIO, Aline; LATANCIA, Marcela; CASTOLDI, Angela; ANDRADE-OLIVEIRA, Vinicius; SILVA, Eloisa Martins da; HIYANE, Meire Ioshie; PEREIRA, Alexandre da Costa; FESTUCCIA, William; MEOTTI, Flavia Carla; CAMARA, Niels Olsen Saraiva
    Sepsis is a complex infectious syndrome in which neutrophil participation is crucial for patient survival. Neutrophils quickly sense and eliminate the pathogen by using different effector mechanisms controlled by metabolic processes. The mammalian target of rapamycin (mTOR) pathway is an important route for metabolic regulation, and its role in neutrophil metabolism has not been fully understood yet, especially the importance of mTOR complex 2 (mTORC2) in the neutrophil effector functions. In this study, we observed that the loss of Rictor (mTORC2 scaffold protein) in primary mouse-derived neutrophils affects their chemotaxis by fMLF and their microbial killing capacity, but not the phagocytic capacity. We found that the microbicidal capacity was impaired in Rictor-deleted neutrophils because of an improper fusion of granules, reducing the hypochlorous acid production. The loss of Rictor also led to metabolic alterations in isolated neutrophils, increasing aerobic glycolysis. Finally, myeloid-Rictor-deleted mice (LysMRic Delta/Delta) also showed an impairment of the microbicidal capacity, increasing the bacterial burden in the Escherichia coli sepsis model. Overall, our results highlight the importance of proper mTORC2 activation for neutrophil effector functions and metabolism during sepsis.
  • article 4 Citação(ões) na Scopus
    Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients
    (2020) BAPTISTA, A.L.; PADILHA, K.; MALAGRINO, P.A.; VENTURINI, G.; ZERI, A.C.M.; REIS, L.M. dos; MARTINS, J.S.; JORGETTI, V.; PEREIRA, A.C.; TITAN, S.M.; MOYSES, R.M.A.
    Bone biopsy is still the gold standard to assess bone turnover (T), mineralization (M), and volume (V) in CKD patients, and serum biomarkers are not able to replace histomorphometry. Recently, metabolomics has emerged as a new technique that could allow for the identification of new biomarkers useful for disease diagnosis or for the understanding of pathophysiologic mechanisms, but it has never been assessed in the chronic kidney disease–mineral and bone disorder (CKD–MBD) scenario. In this study, we investigated the association between serum metabolites and the bone TMV classification in patients with end-stage renal disease by using serum NMR spectroscopy and bone biopsy of 49 hemodialysis patients from a single center in Brazil. High T was identified in 21 patients and was associated with higher levels of dimethylsulfone, glycine, citrate, and N-acetylornithine. The receiver-operating characteristic curve for the combination of PTH and these metabolites provided an area under the receiver-operating characteristic curve (AUC) of 0.86 (0.76 to 0.97). Abnormal M was identified in 30 patients and was associated with lower ethanol. The AUC for age, diabetes mellitus, and ethanol was 0.83 (0.71 to 0.96). Low V was identified in 17 patients and was associated with lower carnitine. The association of age, phosphate, and carnitine provided an AUC of 0.83 (0.70 to 0.96). Although differences among the curves by adding selected metabolites to traditional models were not statistically significant, the accuracy of the diagnosis according to the TMV classification seemed to be improved. This is the first study to evaluate the TMV classification system in relation to the serum metabolome assessed by NMR spectroscopy, showing that selected metabolites may help in the evaluation of bone phenotypes in CKD–MBD. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
  • conferenceObject
    Cardiac Hypertrophy and Altered Glycolytic Metabolism are Reversed in an Aortic Constriction Mice Model
    (2019) JENSEN, Leonardo; SILVA, Amanda; FARIA, Daniele; VENTURINI, Gabriela; PEREIRA, Alexandre; BUCHPIGUEL, Carlos Alberto; IRIGOYEN, Maria Claudia C.
  • article 27 Citação(ões) na Scopus
    Human cardiomyocytes for drug discovery
    (2018) BIAGI, Diogo Goncalves; GONCALVES, Jessica; CRUVINEL, Estela; DAMIANI, Renata; VALGODE, Flavia; MEDEIROS, Fabiana; MOREIRA, Camila G.; SANTOS, Evelyn; MARCON, Rodrigo; JOAO, Calixto; VENTURINI, Gabriela; PEREIRA, Alexandre; FERREIRA, Eden; MORTARA, Renato A.; VALADARES, Marcos C.
    Introduction: Cardiac drug discovery are based in old methods that use animals, animal cells or modified cells that do not faithfully represent human cardiac phenotypes. Objective: Here, we aimed to show that cardiomyocytes derived from human iPS cells represent a new tool for cardiac drug discovery and could contribute do reduce animal use in research. Method: Generation of human iPS cells derived cardiomyocytes and its use for cardiotoxicity evaluation and infection with T. cruzi for drug discovery. Results: Definition of robust protocol for human iPS cells reprogramming, maintenance and cardiac differentiation. Derivation of high purity cardiomyocytes from hiPSCs that presented toxicity to different doses of doxorubicin and were amenable to infection of T. cruzi. Conclusions: Human cardiomyocytes derived from human iPS cells can be a great tool for drug discovery and can replace several assays done in animals helping to reduce animal use in research.
  • article 2 Citação(ões) na Scopus
    Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature
    (2022) SABINO, Ester Cerdeira; FRANCO, Lucas Augusto Moyses; VENTURINI, Gabriela; RODRIGUES, Mariliza Velho; MARQUES, Emanuelle; SILVA, Lea Campos de Oliveira-da; MARTINS, Larissa Natany Almeida; FERREIRA, Ariela Mota; ALMEIDA, Paulo Emilio Clementino; SILVA, Felipe Dias Da; LEITE, Samara Fernandes; NUNES, Maria do Carmo Pereira; HAIKAL, Desiree Sant'Ana; OLIVEIRA, Claudia Di Lorenzo; CARDOSO, Clareci Silva; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; CASAS, Juan P.; RIBEIRO, Antonio Luiz Pinho; KRIEGER, Jose E.; PEREIRA, Alexandre C.
    Background Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. Methodology/Principal findings We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10(-9)) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. Conclusions/Significance We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.
  • article 19 Citação(ões) na Scopus
    Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease
    (2017) MALAGRINO, Pamella Araujo; VENTURINI, Gabriela; YOGI, Patricia Schneider; DARIOLLI, Rafael; PADILHA, Kallyandra; KIERS, Bianca; GOIS, Tamiris Carneiro; CARDOZO, Karina Helena Morais; CARVALHO, Valdemir Melechco; SALGUEIRO, Jessica Silva; GIRARDI, Adriana Castello Costa; TITAN, Silvia Maria de Oliveira; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa
    The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60 min) and 4, 11 and 16 h post-reperfusion, and renal cortex samples after 24 h of reperfusion. Peptides were analyzed on the Q-Exactive (TM). In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease. Biological significance: The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative biomarkers for this condition have also been identified in a number of other clinical scenarios, such as cardiovascular diseases, chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential biomarkers for kidney disease, using kidney ischemia/reperfusion as a paradigm for a kidney pathological event.