GABRIELA VENTURINI DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
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.- 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 SaraivaSepsis 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.
- Metabolomic Evaluation of Chronic Periodontal Disease in Older Adults(2021) RODRIGUES, Wellington F.; MIGUEL, Camila B.; AGOSTINHO, Ferdinando; V, Gabriela da Silva; LAZO-CHICA, Javier E.; SCAPIN, Sandra M. Naressi; NAPIMOGA, Marcelo H.; TRINDADE-DA-SILVA, Carlos A.; KRIEGER, Jose E.; PEREIRA, Alexandre da Costa; OLIVEIRA, Carlo J. Freire; SOARES, Siomar de Castro; UEIRA-VIEIRA, Carlos; KLEINJAN, AlexPeriodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection score>1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.
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.- Cardiomyocyte infection by Trypanosoma cruzi promotes innate immune response and glycolysis activation(2023) VENTURINI, Gabriela; ALVIM, Juliana M.; PADILHA, Kallyandra; TOEPFER, Christopher N.; GORHAM, Joshua M.; WASSON, Lauren K.; BIAGI, Diogo; SCHENKMAN, Sergio; CARVALHO, Valdemir M.; SALGUEIRO, Jessica S.; CARDOZO, Karina H. M.; KRIEGER, Jose E.; PEREIRA, Alexandre C.; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.IntroductionChagas cardiomyopathy, a disease caused by Trypanosoma cruzi (T. cruzi) infection, is a major contributor to heart failure in Latin America. There are significant gaps in our understanding of the mechanism for infection of human cardiomyocytes, the pathways activated during the acute phase of the disease, and the molecular changes that lead to the progression of cardiomyopathy. MethodsTo investigate the effects of T. cruzi on human cardiomyocytes during infection, we infected induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) with the parasite and analyzed cellular, molecular, and metabolic responses at 3 hours, 24 hours, and 48 hours post infection (hpi) using transcriptomics (RNAseq), proteomics (LC-MS), and metabolomics (GC-MS and Seahorse) analyses. ResultsAnalyses of multiomic data revealed that cardiomyocyte infection caused a rapid increase in genes and proteins related to activation innate and adaptive immune systems and pathways, including alpha and gamma interferons, HIF-1 alpha signaling, and glycolysis. These responses resemble prototypic responses observed in pathogen-activated immune cells. Infection also caused an activation of glycolysis that was dependent on HIF-1 alpha signaling. Using gene editing and pharmacological inhibitors, we found that T. cruzi uptake was mediated in part by the glucose-facilitated transporter GLUT4 and that the attenuation of glycolysis, HIF-1 alpha activation, or GLUT4 expression decreased T. cruzi infection. In contrast, pre-activation of pro-inflammatory immune responses with LPS resulted in increased infection rates. ConclusionThese findings suggest that T. cruzi exploits a HIF-1 alpha-dependent, cardiomyocyte-intrinsic stress-response activation of glycolysis to promote intracellular infection and replication. These chronic immuno-metabolic responses by cardiomyocytes promote dysfunction, cell death, and the emergence of cardiomyopathy.