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Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach

Grant number: 15/03965-2
Support type:Research Projects - Thematic Grants
Duration: February 01, 2016 - January 31, 2022
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal Investigator:Carlos Ferreira dos Santos
Grantee:Carlos Ferreira dos Santos
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Co-Principal Investigators:Sandra Helena Penha de Oliveira ; Vanessa Soares Lara
Assoc. researchers:Ana Lucia Pompeia Fraga de Almeida ; Andrew Seth Greene ; Carla Renata Sipert ; Estevam Augusto Bonfante ; Gustavo Pompermaier Garlet ; Karin Hermana Neppelenbroek ; Luiz Fernando Pegoraro ; Marcia Pinto Alves Mayer ; Maria Aparecida de Andrade Moreira Machado ; Maria Helena Raposo Fernandes ; Marília Afonso Rabelo Buzalaf ; Thais Marchini de Oliveira Valarelli ; Vinicíus Carvalho Porto
Associated scholarship(s):21/00654-7 - Effects of losartan on the concentration of the renin-angiotensin system components in bone and gingival tissues of rats with experimentally induced periodontal disease, BP.IC
20/03068-9 - The role of renin-angiotensin system on bone metabolism of the mandible of diabetic mice with induced-periodontal disease, BP.MS
18/23676-3 - MicroRNAs role in bone impairment induced by periodontal disease and the local renin-angiotensin system in spontaneous hypertensive rats, BP.DR
+ associated scholarships 19/27273-3 - Effect of Alisquiren on alterations of RANK/RANKL/OPG axis in bone loss induced by periodontal disease in diabetic mice, BP.IC
19/26149-7 - Role of Angiotensin II on the in vitro osteoblastic differentiation of SPONTANEALLY HYPERTENSE mice in bone marrow stromal mesenchymal cells, BP.IC
19/20240-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach, BP.TT
19/10344-5 - Inflammatory markers of saliva and gingival sulcus of teeth to receive metal-ceramic crown measured in different stages of clinical procedures and the influence of renin-angiotensin system on treatment, BP.DD
19/01380-8 - Evaluation of the anti-inflammatory effect of nanoparticles of Punica granatum Linné on the human monocyte line THP-1, BP.PD
18/10568-8 - Influence of mast cells on the process of osteoblastic cells differentiation derived from the calvaria of spontaneously hypertensive rats, BP.IC
18/04989-0 - The role of mast cells and their microRNAs on the inflammatory response and bone metabolism in diabetic mice with periodontitis, BP.IC
18/04476-3 - The role of renin on the production of Th17 cytokines, oxidative stress and antioxidants by gingival tissue from diabetic mice with periodontite, BP.IC
18/05050-0 - The role of mast cells and their microRNAs on the inflammatory response and bone metabolism in diabetic mice with periodontitis, BP.TT
17/17747-2 - Qualitative and quantitative analysis of gingival sulcus cytokines in teeth chosen for metal ceramic crowns during different steps of clinical procedures, in patients taking Angiotensin II AT1a receptor antagonists, BP.MS
17/19294-5 - Inhibitor drugs of the renin-angiotensin system: antimicrobial action against Candida albicans, BP.IC
17/19227-6 - Investigation of the modulation of the inflammatory response in human oral and immunological cells by Ang II and Ang 1-7, BP.DR
17/07095-8 - The role of mast cells upon the in vitro osteogenic differentiation of the mesenchymal stromal cells from the bone marrow of mice, BP.IC
17/05873-3 - In vitro analysis of mast cells and renin-angiotensin system role of spontaneously hypertensive animals osteoblasts and osteoclasts, BP.PD
17/02271-2 - The role of Telmisartan in osteoblastic differentiation in spontaneously hypertensive rats, BP.IC
16/16473-3 - Study of the role of angiotensin II on in vitro differentiation of human apical papilla cells, BP.MS
16/11450-5 - Study of the role of renin-angiotensin system components in the immunomodulation of fibroblasts from deciduous dental pulp teeth., BP.PD
16/05780-2 - The role of mast cells and renin-angiotensin system on the inflamatory response induced by experimental periodontitis in mice, BP.IC - associated scholarships

Abstract

In dentistry, there is growing interest in understanding the relationship between the inflammatory response and bone metabolism, especially regarding chronic and infectious diseases. The exploration of possible interactions between oral and systemic health has been shown to be relevant for enabling the understanding of modulators of the inflammatory process, such as the renin-angiotensin system. In this context, this thematic project aims to investigate the molecular aspects of inflammation in different animal and human experimental models, as well as to explore relevant clinical aspects to this proposal. To achieve these goals, we will use different methodologies and approaches which include: 1 - Molecular and biochemical characterization of mediators involved in infectious / inflammatory processes in animal models of experimental periodontitis, denture stomatitis, diabetes and hypertension; 2 - Investigation of important aspects of cellular metabolism, such as cytokines / chemokines / reactive oxygen species release in different models of in vitro cell culture (fibroblasts, epithelial cells, monocytes, mast cells, osteoblasts and osteoclasts); 3- translational aspects related to the axis inflammation / renin-angiotensin through gingival inflammatory response of patients in oral rehabilitation who are antihypertensive drug users. The association of genetic and pharmacological inhibition tools will be used aiming to improve the knowledge in the area and contribute to the development and production of new drugs in the future. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Markers of COVID-19 severity and therapeutic targets possibly unveiled in patients’ blood plasma 
Articles published in other media outlets (52 total):
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Yahoo!: Pesquisadores da USP conseguem identificar gravidade da COVID-19 pelo sangue (03/Feb/2021)
Portal Exame: Pesquisadores da USP identificam gravidade da covid-19 pelo sangue (03/Feb/2021)
Yahoo!: Pesquisadores da USP conseguem identificar gravidade da COVID-19 pelo sangue (02/Feb/2021)
Yahoo!: Pesquisadores da USP conseguem identificar gravidade da COVID-19 pelo sangue (02/Feb/2021)
Jornal da Cidade (Bauru, SP): Pesquisa da FOB identifica proteínas que podem 'prever' piora da Covid-19 (02/Feb/2021)
Estadão.com: Análise sanguínea de pacientes com covid revela possíveis marcadores de gravidade da doença (01/Feb/2021)
UOL: Sangue de pacientes com covid-19 mostra possíveis marcadores de gravidade (01/Feb/2021)
Folha de Pernambuco online: Covid-19: análise sanguínea revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
Portal R7: Covid-19: Análise sanguínea revela possíveis marcadores de gravidade (01/Feb/2021)
IstoÉ Dinheiro online: Sangue de pacientes com Covid-19 pode indicar nível de gravidade da doença, diz USP (01/Feb/2021)
iLeon.com (Espanha): La serología de pacientes de covid-19 revela siete proteínas en el plasma que pueden servir para nuevos tratamientos (25/Feb/2021)
Catalunya Vanguardista (Espanha): Covid: plasma sanguíneo para blancos terapéuticos y biomarcadores (24/Feb/2021)
Programa InfoSalud (Argentina): La serología de pacientes con COVID-19 revela posibles marcadores de gravedad y blancos terapéuticos (18/Feb/2021)
Câmara Municipal de São Paulo: Prevalência do novo coronavírus na população da capital é de 13,9%, aponta novo inquérito sorológico (12/Feb/2021)
Sofis Tecnologia: Sangue de pacientes com covid-19 mostra possíveis marcadores de gravidade. (09/Feb/2021)
Rádio Unesp FM 105,7: Um estudo poderá orientar a futura conduta dos médicos no tratamento de pacientes hospitalizados por Covid-19 (08/Feb/2021)
O Correio do Povo (Jaraguá do Sul, SC) online: Pesquisadores da USP conseguem identificar gravidade da Covid-19 pelo sangue (03/Feb/2021)
O Sul: O sangue de pacientes com coronavírus mostra possíveis marcadores de gravidade (03/Feb/2021)
Brazilian Report: Scientists discover genetic markers that could indicate vulnerability to Covid-19 (03/Feb/2021)
Jornal da Cidade (Bauru, SP) online: Pesquisa da FOB identifica proteínas que podem 'prever' piora da Covid-19 (02/Feb/2021)
O Nortão online: Brasileiros identificam proteínas que podem prever gravidade da Covid-19 (02/Feb/2021)
Investe São Paulo: Pesquisa da FOB identifica proteínas que podem 'prever' piora da Covid-19 (02/Feb/2021)
Canaltech: Pesquisadores da USP conseguem identificar gravidade da COVID-19 pelo sangue (02/Feb/2021)
Metropóles: Brasileiros detectam proteínas no sangue que indicam gravidade da Covid-19 (02/Feb/2021)
O Sul online: O sangue de pacientes com coronavírus mostra possíveis marcadores de gravidade (02/Feb/2021)
Saense: Análise sanguínea de pacientes com COVID-19 revela possíveis marcadores de gravidade e alvos terapêuticos (02/Feb/2021)
Jornal Integração: Brasileiros identificam proteínas que podem prever gravidade da Covid-19 (02/Feb/2021)
Blog Saúde e Dicas: Covid-19: análise sanguínea revela possíveis marcadores de gravidade (02/Feb/2021)
Na Hora Online: Sangue de pacientes com Covid-19 pode indicar nível de gravidade da doença, diz USP (02/Feb/2021)
iMove Web: Covid-19: análise sanguínea revela possíveis marcadores de gravidade (02/Feb/2021)
Portal da Capital AM: Covid-19: Estudo detecta proteínas no sangue que podem prever gravidade da doença (02/Feb/2021)
Terra: Análise sanguínea de pacientes com covid revela possíveis marcadores de gravidade da doença (01/Feb/2021)
MSN: Análise sanguínea de pacientes com covid revela possíveis marcadores de gravidade da doença (01/Feb/2021)
Consecti - Conselho Nacional de Secretários Estaduais para Assuntos de CT&I: Análise sanguínea de pacientes com Covid-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
Nominuto.com: Análise sanguínea de pacientes com covid revela possíveis marcadores de gravidade da doença (01/Feb/2021)
Revista Amazônia: Análise sanguínea de pacientes com COVID-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
NewsLab online: Análise sanguínea de pacientes com COVID-19 (01/Feb/2021)
Galileu online: Análise brasileira revela possíveis marcadores de gravidade da Covid-19 (01/Feb/2021)
LabNetwork: Análise sanguínea de pacientes com Covid-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
Jornal da Ciência online: Análise sanguínea de pacientes com covid-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
Jornal Joseense News: Análise sanguínea de pacientes com Covid-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
Piauí Noticias: Covid-19: análise sanguínea revela possíveis marcadores de gravidade (01/Feb/2021)
Portal da Enfermagem: Análise sanguínea de pacientes com Covid-19 revela possíveis marcadores de gravidade e alvos terapêuticos (01/Feb/2021)
TV Assembleia - Assembleia Legislativa do Piauí (Alepi): Sangue de pacientes com Covid-19 pode indicar nível de gravidade da doença, diz USP (01/Feb/2021)
Time 24 News (EUA): Blood from patients with covid-19 shows possible severity markers (01/Feb/2021)
Head Topics (Espanha): Análise sanguínea de pacientes com covid revela possíveis marcadores de gravidade da doença (01/Feb/2021)
Sanar Med: Análise sanguínea revela possíveis marcadores de gravidade e alvos terapêuticos de pacientes com COVID-19 (01/Feb/2021)
Portal Novo Norte: Análise sanguínea pode identificar proteínas relacionadas às complicações da Covid19 (02/Jan/2021)
Enfermagem Piauí: Análise sanguínea de pacientes com COVID-19 revela possíveis marcadores de gravidade e alvos terapêuticos (02/Jan/2021)
Michel Teixeira: Pesquisadores da USP conseguem identificar gravidade da Covid-19 pelo sangue (03/Feb/2021)
Tech Na Net: Pesquisadores da USP conseguem identificar gravidade da COVID-19 pelo sangue (03/Feb/2021)
Pirajuí : Pesquisa da FOB identifica proteínas que podem 'prever' piora da Covid-19 (02/Feb/2021)

Scientific publications (19)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HERRERA, NAIARA A.; DUCHATSCH, FRANCINE; TARDELLI, LIDIELI P.; DIONISIO, THIAGO J.; SANTOS, CARLOS F.; AMARAL, SANDRA L. Dexamethasone Does Not Inhibit Treadmill Training-Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway. Journal of Cardiovascular Pharmacology, v. 76, n. 6, p. 708-714, DEC 2020. Web of Science Citations: 0.
BRITO, VICTOR GUSTAVO BALERA; PATROCINIO, MARIANA SOUSA; DE SOUSA, MARIA CAROLINA LINJARDI; BARRETO, AYNA EMANUELLI ALVES; FRASNELLI, SABRINA CRUZ TFAILE; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; OLIVEIRA, SANDRA HELENA PENHA. Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease. FRONTIERS IN PHARMACOLOGY, v. 11, NOV 11 2020. Web of Science Citations: 0.
PINKE, KAREN HENRIETTE; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; LARA, VANESSA SOARES; SARTORI, ALEXANDRINA. Should mast cells be considered therapeutic targets in multiple sclerosis?. NEURAL REGENERATION RESEARCH, v. 15, n. 11, p. 1995-2007, NOV 2020. Web of Science Citations: 0.
DUCHATSCH, FRANCINE; TARDELLI, LIDIELI P.; HERRERA, NAIARA A.; RUIZ, THALLES F. R.; VICENTINI, CARLOS A.; OKOSHI, KATASHI; SANTOS, CARLOS F.; AMARAL, SANDRA L. Dexamethasone and Training-Induced Cardiac Remodeling Improve Cardiac Function and Arterial Pressure in Spontaneously Hypertensive Rats. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, v. 26, n. 2 AUG 2020. Web of Science Citations: 0.
DA SILVA, RAFAELA ALVES; COLOMBINI ISHIKIRIAMA, BELLA LUNA; RIBEIRO LOPES, MARCELO MILANDA; DE CASTRO, RICARDO DIAS; GARCIA, CINDY RUIZ; PORTO, VINICIUS CARVALHO; SANTOS, CARLOS FERREIRA; NEPPELENBROEK, KARIN HERMANA; LARA, VANESSA SOARES. Antifungal activity of Punicalagin-nystatin combinations againstCandida albicans. ORAL DISEASES, JUL 2020. Web of Science Citations: 0.
COLOMBINI-ISHIKIRIAMA, BELLA LUNA; DIONISIO, THIAGO JOSE; GARBIERI, THAIS FRANCINI; DA SILVA, RAFAELA ALVES; ANDRADE MOREIRA MACHADO, MARIA APARECIDA; PENHA DE OLIVEIRA, SANDRA HELENA; LARA, VANESSA SOARES; GREENE, ANDREW SETH; SANTOS, CARLOS FERREIRA. What is the response profile of deciduous pulp fibroblasts stimulated withE. coliLPS andE. faecalisLTA?. BMC IMMUNOLOGY, v. 21, n. 1 JUN 22 2020. Web of Science Citations: 0.
KARIN CRISTINA DA SILVA MODENA; ADRIANA MARIA CALVO; CARLA RENATA SIPERT; BELLA LUNA COLOMBINI-ISHIKIRIAMA; THIAGO JOSÉ DIONÍSIO; MARIA FIDELA DE LIMA NAVARRO; MARIA TERESA ATTA; CARLOS FERREIRA SANTOS. Molecular Response of Pulp Fibroblasts after Stimulation with Pulp Capping Materials. Brazilian Dental Journal, v. 31, n. 3, p. 244-251, Jun. 2020.
PIZZATTO, LAIS NICOLAY; MENESES, CLAUDIA C. B.; DINIZ, ELISA A.; DIONISIO, THIAGO J.; SANTOS, CARLOS FERREIRA; SIPERT, CARLA R. Angiotensin II Regulates Proliferation and Function of Stem Cells of Apical Papilla. JOURNAL OF ENDODONTICS, v. 46, n. 6, p. 810-817, JUN 2020. Web of Science Citations: 0.
HERRERA, NAIARA A.; DUCHATSCH, FRANCINE; TARDELLI, LIDIELI P.; DIONISIO, THIAGO J.; SHINOHARA, ANDRE L.; SANTOS, CARLOS F.; AMARAL, SANDRA LIA. MicroRNA-126 upregulation, induced by training, plays a role in controlling microcirculation in dexamethasone treated rats. Molecular and Cellular Endocrinology, v. 505, APR 5 2020. Web of Science Citations: 0.
DIONISIO, THIAGO J.; SOUZA, GABRIELA P.; COLOMBINI-ISHIKIRIAMA, BELLA L.; GARBIERI, THAIS F.; PARISI, VIVIANE A.; OLIVEIRA, GABRIELA M.; CANO, ISADORA P.; RODINI, CAMILA O.; OLIVEIRA, SANDRA H. P.; GREENE, ANDREW S.; SANTOS, CARLOS F. AT1 receptor antagonism promotes bone loss attenuation in experimental periodontitis, blocks inflammatory mediators, and upregulates antioxidant enzymes and bone formation markers. Journal of Periodontology, v. 91, n. 4, p. 533-544, APR 2020. Web of Science Citations: 0.
FABRICIO, MAYARA F.; JORDAO, MARIA T.; MIOTTO, DANYELLE S.; RUIZ, THALLES F. R.; VICENTINI, CARLOS A.; LACCHINI, SILVIA; SANTOS, CARLOS FERREIRA; MICHELINI, LISETE C.; AMARAL, SANDRA L. Standardization of a new non-invasive device for assessment of arterial stiffness in rats: Correlation with age-related arteries' structure. METHODSX, v. 7, 2020. Web of Science Citations: 0.
PENHA OLIVEIRA, SANDRA HELENA; BALERA BRITO, VICTOR GUSTAVO; TFAILE FRASNELLI, SABRINA CRUZ; RIBEIRO, BIANCA DA SILVA; FERREIRA, MILENA NUNES; QUEIROZ, DAYANE PRISCILLA; BELTAN, CARLUCI TAIS; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA. Aliskiren Attenuates the Inflammatory Response and Wound Healing Process in Diabetic Mice With Periodontal Disease. FRONTIERS IN PHARMACOLOGY, v. 10, JUL 4 2019. Web of Science Citations: 1.
CASAROTO, ANA REGINA; DA SILVA, RAFAELA ALVES; SALMERON, SAMIRA; RUBO DE REZENDE, MARIA LUCIA; DIONISIO, THIAGO JOSE; DOS SANTOS, CARLOS FERREIRA; PINKE, KAREN HENRIETTE; GUARIZO KLINGBEIL, MARIA FATIMA; SALOMAO, PRISCILA ARANDA; RIBEIRO LOPES, MARCELO MILANDA; LARA, VANESSA SOARES. Candida albicans-Cell Interactions Activate Innate Immune Defense in Human Palate Epithelial Primary Cells via Nitric Oxide (NO) and (3-Defensin 2 (hBD-2). CELLS, v. 8, n. 7 JUL 2019. Web of Science Citations: 0.
CANO, ISADORA PRADO; DIONISIO, THIAGO JOSE; CESTARI, TANIA MARY; CALVO, ADRIANA MARIA; COLOMBINI-ISHIKIRIAMA, BELLA LUNA; CARDOSO FARIA, FLAVIO AUGUSTO; SIQUEIRA, WALTER LUIZ; SANTOS, CARLOS FERREIRA. Losartan and isoproterenol promote alterations in the local renin-angiotensin system of rat salivary glands. PLoS One, v. 14, n. 5 MAY 22 2019. Web of Science Citations: 0.
RAHHAL, JULIANA GARUBA; ROVAI, EMANUEL DA SILVA; HOLZHAUSEN, MARINELLA; CALDEIRA, CELSO LUIZ; DOS SANTOS, CARLOS FERREIRA; SIPERT, CARLA RENATA. Root canal dressings for revascularization influence in vitro mineralization of apical papilla cells. Journal of Applied Oral Science, v. 27, 2019. Web of Science Citations: 0.
DUCHATSCH, FRANCINE; CONSTANTINO, PAULA B.; HERRERA, NAIARA A.; FABRICIO, MAYARA F.; TARDELLI, LIDIELI P.; MARTUSCELLI, ALINE M.; DIONISIO, THIAGO J.; SANTOS, CARLOS F.; AMARAL, SANDRA L. Short-term exposure to dexamethasone promotes autonomic imbalance to the heart before hypertension. JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION, v. 12, n. 8, p. 605-613, AUG 2018. Web of Science Citations: 0.
DA SILVA, ROBERTA FERNANDA; LACCHINI, RICCARDO; PINHEIRO, LUCAS CEZAR; DIONISIO, THIAGO JOSE; JACOMINI, ANDRE MOURAO; TANUS-SANTOS, JOSE EDUARDO; AMARAL, SANDRA LIA; SANTOS, CARLOS FERREIRA; ZAGO, ANDERSON SARANZ. Preliminary study about the relationship between estimated training status and RAS polymorphisms on blood pressure and ACE activity in the elderly. JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, v. 19, n. 2 JUN 20 2018. Web of Science Citations: 0.
MARTINS ALMEIDA, NARA LIGIA; SALDANHA, LUIZ LEONARDO; DA SILVA, RAFAELA ALVES; PINKE, KAREN HENRIETTE; DA COSTA, ELIANE FERRAZ; PORTO, VINICIUS CARVALHO; DOKKEDAL, ANNE LIGIA; LARA, VANESSA SOARES. Antimicrobial activity of denture adhesive associated with Equisetum giganteum- and Punica granatum-enriched fractions against Candida albicans biofilms on acrylic resin surfaces. BIOFOULING, v. 34, n. 1, p. 62-73, 2018. Web of Science Citations: 0.
GABRIELE, LILIAN GOBBO; MORANDINI, ANA CAROLINA; DIONISIO, THIAGO JOSE; SANTOS, CARLOS FERREIRA. Angiotensin II Type 1 Receptor Knockdown Impairs Interleukin-1 beta-Induced Cytokines in Human Periodontal Fibroblasts. Journal of Periodontology, v. 88, n. 1, p. E1-E11, JAN 2017. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.