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

• Grant number: 15/03965-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2016
• End date: April 30, 2022
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Carlos Ferreira dos Santos
• Grantee: Carlos Ferreira dos Santos
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Pesquisadores principais: Sandra Helena Penha de Oliveira ; Vanessa Soares Lara
• Associated 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 research grant(s): 23/13957-3 - 18th International Congress of Immunology, AR.EXT
• Associated scholarship(s): 21/10042-9 - Role of AT1 and AT2 receptors in osteogenic differentiation in rats periodontal ligament cells, BP.MS; 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; + associated scholarships 18/23676-3 - MicroRNAs role in bone impairment induced by periodontal disease and the local renin-angiotensin system in spontaneous hypertensive rats, BP.DR; 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 - Periodontal reaction induced by the clinical steps of metalloceramic crowns considering how the renin-angiotensin system influences treatment and salivation, 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)

Scientific publications

(28)

(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)

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. (15/03965-2)

DA SILVA, ROBERTA FERNANDA; LACCHINI, RICCARDO; PINHEIRO, LUCAS CEZAR; FEREZIN, LETICIA PERTICARRARA; TANUS-SANTOS, JOSE EDUARDO; LUIZON, MARCELO RIZZATTI; DIONISIO, THIAGO JOSE; SANTOS, CARLOS FERREIRA; REIA, THAIS AMANDA; JACOMINI, ANDRE MOURAO; et al. Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study. CLINICAL AND EXPERIMENTAL HYPERTENSION, JUN 2021. (15/03965-2, 15/24847-8)

GARBIERI, THAIS FRANCINI; MARTIN, VICTOR; SANTOS, CARLOS FERREIRA; GOMES, PEDRO DE SOUSA; FERNANDES, MARIA HELENA. The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue. PHARMACEUTICALS, v. 14, n. 5, MAY 2021. (15/03965-2, 17/19227-6, 18/23934-2)

BARRETO, AYNA EMANUELLI ALVES; BRITO, VICTOR GUSTAVO BALERA; PATROCINIO, MARIANA SOUSA; BALLASSONI, BEATRIZ BABETO; FRASNELLI, SABRINA CRUZ TFAILE; OLIVEIRA, SANDRA HELENA PENHA. beta 1-adrenergic receptor but not beta 2 mediates osteogenic differentiation of bone marrow mesenchymal stem cells in normotensive and hypertensive rats. European Journal of Pharmacology, v. 911, NOV 15 2021. (15/03965-2, 17/05873-3)

BALERA BRITO, VICTOR GUSTAVO; PATROCINIO, MARIANA SOUSA; LINJARDI SOUSA, MARIA CAROLINA; ALVES BARRETO, AYNA EMANUELLI; TFAILE FRASNELLI, SABRINA CRUZ; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; PENHA OLIVEIRA, SANDRA HELENA. Mast cells contribute to alveolar bone loss in Spontaneously Hypertensive Rats with periodontal disease regulating cytokines production. PLoS One, v. 16, n. 3, MAR 4 2021. (18/23676-3, 17/05873-3, 17/07095-8, 17/02271-2, 15/03965-2)

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. (14/23050-6, 15/03965-2, 12/19722-3, 14/23229-6)

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. (18/04989-0, 17/05873-3, 18/04476-3, 15/03965-2)

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. (15/09750-8, 15/03965-2, 16/13944-5, 15/11587-8)

OLIVEIRA, GABRIELA MORAES; DIONISIO, THIAGO JOSE; FLEURY, CAMILA ASSIS; CALVO, ADRIANA MARIA; SANTOS, CARLOS FERREIRA; CARDOSO FARIA, FLAVIO AUGUSTO. Is It Safe to Use Vasoconstrictors in Association Treated with Amitriptyline or Can It Potentiate Cardiovascular Effects? In Vivo Animal Study. APPLIED SCIENCES-BASEL, v. 12, n. 23, p. 10-pg., 2022-12-01. (17/12725-0, 15/03965-2)

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. (12/12458-9, 14/07012-7, 15/03965-2)

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. (15/24847-8, 15/03965-2)

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. (18/06998-7, 17/14405-3, 16/12532-5, 17/00509-1, 15/03965-2)

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. (18/14544-6, 14/23229-6, 15/03965-2, 17/00509-1)

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, v. 26, n. 8, p. 1810-1819, NOV 2020. (15/03965-2)

PINHO, LAURA COSTA; GARBIERI, THAIS FRANCINI; GRENHO, LILIANA; ALVES, MARTA M.; SOUSA GOMES, PEDRO; SANTOS, CARLOS FERREIRA; FERNANDES, MARIA HELENA; SANTOS, CATARINA; COLACO, BRUNO. Rosehip Extract-Functionalized Magnesium Hydroxide Nanoparticles and Its Effect on Osteoblastic and Osteoclastic Cells. MATERIALS, v. 14, n. 15, AUG 2021. (15/03965-2, 17/19227-6, 18/23934-2)

DA SILVA, ROBERTA FERNANDA; LACCHINI, RICCARDO; PINHEIRO, LUCAS CEZAR; FEREZIN, LETICIA PERTICARRARA; TANUS-SANTOS, JOSE EDUARDO; LUIZON, MARCELO RIZZATTI; DIONISIO, THIAGO JOSE; SANTOS, CARLOS FERREIRA; REIA, THAIS AMANDA; JACOMINI, ANDRE MOURAO; et al. Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study. CLINICAL AND EXPERIMENTAL HYPERTENSION, v. 43, n. 7, p. 661-670, OCT 3 2021. (15/24847-8, 15/03965-2)

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.; et al. 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. (15/03965-2)

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. (14/12975-9, 14/22379-4, 17/17747-2, 15/03965-2)

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. (13/16113-9, 15/03965-2, 15/20954-4)

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. (17/02271-2, 18/23676-3, 17/05873-3, 17/07095-8, 15/03965-2)

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; et al. 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. (11/17481-6, 15/03965-2)

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. (16/11450-5, 15/03965-2)

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, 2020-07-13. (05/60167-0, 15/03965-2, 10/01230-1)

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. (15/03965-2, 14/00239-6)

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. (18/06998-7, 17/00509-1, 16/12532-5, 17/14405-3, 15/03965-2)

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. (17/01737-8, 16/16473-3, 16/13944-5, 15/03965-2)

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. (18/00567-4, 15/03965-2, 17/14405-3, 17/00509-1)

BRITO, VICTOR GUSTAVO BALERA; PATROCINIO, MARIANA SOUSA; BARRETO, AYNA EMANUELLI ALVES; FRASNELLI, SABRINA CRUZ TFAILE; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; OLIVEIRA, SANDRA HELENA PENHA. Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats. European Journal of Pharmacology, v. 912, DEC 5 2021. (17/02271-2, 15/03965-2, 17/05873-3, 18/23676-3)