LUIZ FERNANDO FERRAZ DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Lung ECM composition, its influence factors and transcriptomics in the lungs of severe COVID-19.(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Toledo Do; BRITO, Jose Mara De; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; MONTEIRO, Renata Aparecida De Almeida; DUARTE NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz Da; DOLHNIKOFF, Marisa; MAUAD, Thais
- Dynamics and Heterogeneity of the Lung Immunopathology in Severe COVID-19(2022) ERJEFALT, J.; COSTA, N. De Souza Xavier; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. De Almeida; PINHO, J. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; MONTEIRO, J. Sirino; SETUBAL, J.; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.
- Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model(2017) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; ALEMANY, Adair Aparecida dos Santos; BELOTTI, Luciano; ZATI, Douglas Hidalgo; CAVALCANTE, Marcela Frota; VERAS, Mariana Matera; RIBEIRO, Susan; KALLAS, Esper Georges; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOTT, Marisa; SILVA, Luiz Fernando Ferraz daBackground and objective Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35 - 46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects. Methods Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points. Results The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression. Conclusion We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.
- Air pollution impairs recovery and tissue remodeling in a murine model of acute lung injury(2020) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; ALEMANY, Adair Aparecida dos Santos; BELOTTI, Luciano; SCHALCH, Alexandre Santos; CAVALCANTE, Marcela Frota; RIBEIRO, Susan; VERAS, Mariana Matera; KALLAS, Esper Georges; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; SILVA, Luiz Fernando Ferraz daEvidence regarding the impact of air pollution on acute respiratory distress syndrome (ARDS) is limited, and most studies focus on ARDS onset. Our study aimed to evaluate whether exposure to fine particulate matter interferes with lung recovery and remodeling in a murine model of acute lung injury. Forty-eight mice received nebulized LPS or the vehicle (controls). Blood, BALF, lungs and spleen were collected after 5 weeks of exposure to either PM2.5 (PM and LPS+PM group) or filtered air (control and LPS5w groups). Inflammatory cells and cytokines were assessed in the blood, BALF, lungs and spleen. Stereological analyses and remodeling assessments were performed by histology. The LPS+PM group showed increased BALF leukocytes, characterized by increased macrophages, increased IL-1 beta and IL-6 levels, anemia and thrombocytopenia. Moreover, we also observed septal thickening, decreased alveolar air space total volume and, septa surface density. Finally, regarding tissue remodeling, we observed elastosis of the lung parenchyma, and unlike in the LPS5w group, we did not observe fibrosis in the LPS+PM group. In conclusion, the delayed inflammation resolution due to subchronic exposure to PM2.5 could be influenced by low systemic and local lymphocyte counts, which lead to impaired lung injury recovery and tissue remodeling.
- RAGE expression in lung tissue of ARDS and septic patients(2020) COSTA, Natalia de Souza Xavier; SIGRIST, Giovana Costa; DOLHNIKOFF, Marisa; SILVA, Luiz Fernando Ferraz Da
- Differentially expressed genes in Diffuse Alveolar Damage (DAD) patterns of COVID-19.(2022) COSTA, N. de Souza Xavier; MONTEIRO, J. Sirino; ERJEFALT, J.; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. Almeida; PINHO, J. R. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. F. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.; SETUBAL, J. C.
- COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, ThaisBackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
- Expression patterns of Interleukin-33 and its receptor ST2 in severe COVID-19(2023) LINDO, Caroline; COSTA, Natalia De Souza Xavier; SIDDHURAJ, Premkumar; JONSSON, Jimmie; ORENGO, Jamie M.; SLEEMAN, Matthew A.; LINDSTEDT, Sandra; ANDERSSON, Cecilia; SILVA, Luiz Fernando; DUARTENETO, Armaro Nunes; SALDIVA, Paulo Hilario Nascimento; SANDEN, Caroline; MAUAD, Thais; ERJEFALT, Jonas
- Pulmonary remodeling after ARDS: a new experimental model(2019) GONCALVES, Cintia Tokio Reis; GONCALVES, Carlos Gustavo Oliveira Reis; COSTA, Natalia De S. X.; RIBEIRO, Gabriel; ASSIS, Edson F. De; SILVA, Luiz Fernando F. Da; CALDINI, Elia Garcia; FARIA-NETO, Hugo Caire C.; DOLHNIKOFF, Marisa
- LPS Response Is Impaired by Urban Fine Particulate Matter(2022) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; ALEMANY, Adair Aparecida dos Santos; BELOTTI, Luciano; CAVALCANTE, Marcela Frota; RIBEIRO, Susan; VERAS, Mariana Matera; KALLAS, Esper Georges; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; SILVA, Luiz Fernando Ferraz daFine particulate matter (PM2.5) is a complex mixture of components with diverse chemical and physical characteristics associated with increased respiratory and cardiovascular diseases mortality. Our study aimed to investigate the effects of exposure to concentrated PM2.5 on LPS-induced lung injury onset. BALB/c male mice were exposed to either filtered air or ambient fine PM2.5 in an ambient particle concentrator for 5 weeks. Then, an acute lung injury was induced with nebulized LPS. The animals were euthanized 24 h after the nebulization to either LPS or saline. Inflammatory cells and cytokines (IL-1 beta, IL-4, IL-5, IL-6, IL-10, IL-17, TNF) were assessed in the blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, lung morphology was assessed by stereological methods. Our results showed that the PM+LPS group showed histological evidence of injury, leukocytosis with increased neutrophils and macrophages, and a mixed inflammatory response profile, with increased KC, IL-6, IL-1 beta, IL-4, and IL-17. Our analysis shows that there is an interaction between the LPS nebulization and PM2.5 exposure, differently modulating the inflammatory response, with a distinct response pattern as compared to LPS or PM2.5 exposure alone. Further studies are required to explain the mechanism of immune modulation caused by PM2.5 exposure.