Renin angiotensin and kallikrein kinin systems in hypertension, obesity, diabetes, desnutrition and sepsis: molecular, cellular and physiopathologic mechanisms

• Grant number: 10/51904-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2011
• End date: June 30, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Dulce Elena Casarini
• Grantee: Dulce Elena Casarini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Fernanda Klein Marcondes ; Lisete Compagno Michelini ; Mirian Aparecida Boim
• Associated scholarship(s): 14/23852-5 - Modulation of Angiotensin-(1-7)/Mas axis on diabetic model: the role of stem cells on renal and cardiovascular inflammation, BP.PD; 14/01629-2 - Effect of chronic treatment with everolimus on arterial blood pressure and renal renin angiotensin system in spontaneously hypertensive rats, BP.PD; 14/14744-4 - Chronic stress action on metabolic effects and glycogen content and GLUT4 expression in rat heart, BP.IC; + associated scholarships 13/03543-5 - Time dependent evaluation of potential protein biomarkers in spontaneously diabetic mice, BP.IC; 13/03542-9 - Evaluation of glucose transporters GLUT1 and GLUT4 in spontaneously diabetic mice cardiomyocytes primary culture, BP.IC; 12/22278-8 - Proteomic analysis of the effects of Aloe barbadensis in the kidney of streptozotocin-induced diabetic rats, BP.DD; 12/11698-6 - Evaluation of renal function in the juvenile obesity induced by fat diet after weaning in rats: role of the renin angiotensin system, BP.DD; 11/12971-5 - Identification of potential biomarkers in urine and plasma of spontaneously diabetic mice, BP.PD; 11/14548-2 - Role of I / D polymorphism of the ACE gene and diabetes on the renin-angiotensin and kallikrein kinin systems in renal tissue, BP.DR; 11/13058-1 - Functional evaluation of angiotensin convertin enzyme (ACE) by site-directed changes, BP.DR - associated scholarships

Abstract

The renin angiotensin system (RAS) is recognized as a powerful determinant of homeostasis and cardiovascular and renal hemodynamics. The relationship between the RAS physiology and renal and cardiovascular diseases is far from being understood. Cardiovascular diseases are responsible for high morbidity and mortality index in most countries. Among the various risk factors are the topics addressed in this project, namely, hypertension, obesity, diabetes. The influence of renin angiotensin system on the cardiovascular and renal functions is extremely complex, involving multiple mediators, receptors and different intracellular signaling mechanisms. This project aims to continue and to propose new studies about the role of this system in the pathophysiology of hypertension, obesity, diabetes, malnutrition and sepsis in the topics listed below: l) Markers of the Renin Angiotensin System in Hypertension and Obesity: The association between hypertension, obesity and diabetes is now a major public health problem. The knowledge of biological markers that can be used in the diagnosis and prognosis of these disease is extremely important for the development and improvement of prophylactic and therapeutic methods. Since the RAS is involved in cardiovascular and metabolic alterations evidenced in hypertensive, obese and diabetic patients, we aimed to evaluate the components of the RAS and their polymorphisms in hypertensive patients, obese children and children with low body weight at birth that is a risk for cardiovascular disease. In these studies we will also evaluate the presence of the N-domain ACE isoform with 90kDa, described as biological marker of hypertension; 2) Participation of the RAS in hypertension, diabetes, malnutrition and sepsis: physiologic mechanisms: Whereas animal models are an important experimental tool to complement the clinical and epidemiological studies in this topic, we different approaches; 4) Modulatory effects of exercise on hypertension and diabetes: considering the beneficial effects of exercise in the treatment of hypertension and diabetes we will study the modulatory effects of physical exercise on the Kallikrein-Kinin System and RAS in hypertensive patients, spontaneously hypertensive rats and rats previously exposed to malnutrition in utero. (AU)

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)

BERTONCELLO, NADIA; MOREIRA, ROSELI PERES; ARITA, DANIELLE YURI; ARAGAO, DANIELLE S.; MIZUNO WATANABE, INGRID KAZUE; DANTAS, PATRICIA S.; SANTOS, RALMONY; MATTAR-ROSA, RODOLFO; YOKOTA, RODRIGO; CUNHA, TATIANA SOUSA; et al. Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1-7) and Bradykinin. JOURNAL OF DIABETES RESEARCH, 2015. (10/51904-9, 11/14548-2)

OLIVEIRA, VANESSA; AKAMINE, ELIANA HIROMI; CARVALHO, MARIA HELENA C.; MICHELINI, LISETE COMPAGNO; FORTES, ZULEICA BRUNO; CUNHA, TATIANA SOUSA; FRANCO, MARIA DO CARMO. Influence of Aerobic Training on the Reduced Vasoconstriction to Angiotensin II in Rats Exposed to Intrauterine Growth Restriction: Possible Role of Oxidative Stress and AT(2) Receptor of Angiotensin II. PLoS One, v. 9, n. 11, NOV 18 2014. (07/58044-2, 10/51904-9)

JARA, ZAIRA PALOMINO; ICIMOTO, MARCELO YUDI; YOKOTA, RODRIGO; RIBEIRO, AMANDA APARECIDA; DOS SANTOS, FERNANDO; DE SOUZA, LEANDRO EZEQUIEL; WATANABE, INGRID KAZUE MIZUNO; FRANCO, MARIA DO CARMO; PESQUERO, JORGE LUIZ; IRIGOYEN, MARIA CLAUDIA; et al. Tonin Overexpression in Mice Diminishes Sympathetic Autonomic Modulation and Alters Angiotensin Type 1 Receptor Response. FRONTIERS IN MEDICINE, v. 5, JAN 23 2019. (10/51904-9)

FERREIRA, NAOMI VIDAL; CUNHA, PAULO JANNUZZI; DA COSTA, DANIELLE IRIGOYEN; DOS SANTOS, FERNANDO; COSTA, FERNANDO OLIVEIRA; CONSOLIM-COLOMBO, FERNANDA; IRIGOYEN, MARIA CLAUDIA. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle-brachial index. CLINICAL INTERVENTIONS IN AGING, v. 10, p. 839-847, 2015. (07/58942-0, 10/51904-9)

DE ALMEIDA CHAVES RODRIGUES, ALINE FERNANDA; BRITES DE LIMA, INGRID LAUREN; BERGAMASCHI, CASSIA TOLEDO; CAMPOS, RUY RIBEIRO; HIRATA, APARECIDA EMIKO; MARIA SCHOORLEMMER, GUUS HERMANUS; GOMES, GUIOMAR NASCIMENTO. Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 304, n. 2, p. F189-F197, JAN 2013. (10/51904-9)

ANDREA SANCHES; RAFAELA COSTA; FERNANDA KLEIN MARCONDES; TATIANA SOUSA CUNHA. Relação entre estresse, depressão, alterações cardiometabólicas e exercício físico. Fisioter. mov., v. 29, n. 1, p. 23-36, 2016-03-00. (10/51904-9)

RIBEIRO, AMANDA A.; AMORIM, REBECA PADRAO; PALOMINO, ZAIRA J.; LIMA, MERCIA DE PAULA; MORAES-SILVA, IVANA CINTHYA; SOUZA, LEANDRO EZEQUIEL; PESQUERO, JORGE LUIZ; IRIGOYEN, MARIA CLAUDIA; CASARINI, DULCE E.. (Pro)renin receptor expression in myocardial infarction in transgenic mice expressing rat tonin. International Journal of Biological Macromolecules, v. 108, p. 817-825, MAR 2018. (10/19989-4, 10/51904-9)

COSTA, RAFAELA; TAMASCIA, MARIANA LEITE; SANCHES, ANDREA; MOREIRA, ROSELI PERES; CUNHA, TATIANA SOUSA; NOGUEIRA, MARIE DOKI; CASARINI, DULCE ELENA; MARCONDES, FERNANDA KLEIN. Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II. Behavioural Brain Research, v. 379, FEB 3 2020. (10/51904-9)

SILVA, JR., SEBASTIAO D.; JARA, ZAIRA P.; PERES, ROSELI; LIMA, LARISSA S.; SCAVONE, CRISTOFORO; MONTEZANO, AUGUSTO C.; TOUYZ, RHIAN M.; CASARINI, DULCE E.; MICHELINI, LISETE C.. Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction. PLoS One, v. 12, n. 12, DEC 12 2017. (11/15681-8, 10/51904-9, 11/51410-9)

LEITE, A. P. O.; ARAGAO, DANIELLE S.; NOGUEIRA, MARIE D.; PEREIRA, RENATA O.; JARA, ZAIRA P.; FIORINO, PATRICIA; CASARINI, DULCE E.; FARAH, VERA. Modulation of reninangiotensin system components by high glucose levels in the culture of collecting duct cells. Journal of Cellular Physiology, v. 234, n. 12, p. 22809-22818, DEC 2019. (10/51904-9)

COSTA, RAFAELA; CARVALHO, MAELINE SANTOS MORAIS; BRANDAO, JULIANA DINEIA PEREZ; MOREIRA, ROSELI PERES; CUNHA, TATIANA SOUSA; CASARINI, DULCE ELENA; MARCONDES, FERNANDA KLEIN. Modulatory action of environmental enrichment on hormonal and behavioral responses induced by chronic stress in rats: Hypothalamic renin-angiotensin system components. Behavioural Brain Research, v. 397, JAN 15 2021. (10/51904-9)

BASTOS, DANIELA B.; SARAFIM-SILVA, BRUNA A. M.; SUNDEFELD, MARIA LUCIA M. M.; RIBEIRO, AMANDA A.; BRANDAO, JULIANA D. P.; BIASOLI, EDER R.; MIYAHARA, I, GLAUCO; CASARINI, DULCE E.; BERNABE, DANIEL G.. Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients. PLoS One, v. 13, n. 8, AUG 20 2018. (16/25255-0, 15/12485-4, 10/51904-9)

JARA, ZAIRA PALOMINO; FIORINO, PATRICIA. Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model. FRONTIERS IN PHYSIOLOGY, v. 9, OCT 10 2018. (10/51904-9)

ARAGAO, DANIELLE S.; DE ANDRADE, MARIA CLAUDINA C.; EBIHARA, FABIANA; WATANABE, INGRID K. M.; MAGALHAES, DAYANE C. B. P.; JULIANO, MARIA APARECIDA; HIRATA, IZAURA YOSHICO; CASARINI, DULCE ELENA. Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme. International Journal of Biological Macromolecules, v. 72, p. 673-679, JAN 2015. (10/51904-9)

ROSA, RODOLFO MATTAR; COLUCCI, JULIANA ALMADA; YOKOTA, RODRIGO; MOREIRA, ROSELI PERES; ARAGAO, DANIELLE SANCHES; RIBEIRO, AMANDA APARECIDA; ARITA, DANIELLE YURI; MIZUNO WATANABE, INGRID KAZUE; PALOMINO, ZAIRA; CUNHA, TATIANA SOUSA; et al. Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 311, n. 3, p. F496-F504, SEP 1 2016. (10/51904-9, 11/04940-2)

SILVA, JR., SEBASTIAO D.; ZAMPIERI, THAIS T.; RUGGERI, ADRIANA; CERONI, ALEXANDRE; ARAGAO, DANIELLE S.; FERNANDES, FERNANDA B.; CASARINI, DULCE E.; MICHELINI, LISETE C.. Downregulation of the Vascular Renin-Angiotensin System by Aerobic Training - Focus on the Balance Between Vasoconstrictor and Vasodilator Axes. CIRCULATION JOURNAL, v. 79, n. 6, p. 1372-1380, JUN 2015. (11/15681-8, 10/51904-9)

COSTA, RAFAELA; TAMASCIA, MARIANA L.; NOGUEIRA, MARIE D.; CASARINI, DULCE E.; MARCONDES, FERNANDA K.. Handling of Adolescent Rats Improves Learning and Memory and Decreases Anxiety. Journal of the American Association for Laboratory Animal Science, v. 51, n. 5, p. 548-553, SEP 2012. (10/51904-9)

MALUF-MEIKEN, LEILA C. V.; FERNANDES, FERNANDA B.; ARAGAO, DANIELLE S.; RONCHI, FERNANDA A.; ANDRADE, MARIA C. C.; FRANCO, MARIA C.; FEBBA, ANDREIA C. S.; PLAVNIK, FRIDA L.; KRIEGER, JOSE E.; MILL, JOSE G.; et al. N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study. INTERNATIONAL JOURNAL OF HYPERTENSION, v. 2012, p. 9-pg., 2012-01-01. (02/13290-2, 10/51904-9)

BERTONCELLO, NADIA; MOREIRA, ROSELI PERES; ARITA, DANIELLE YURI; ARAGAO, DANIELLE S.; MIZUNO WATANABE, INGRID KAZUE; DANTAS, PATRICIA S.; SANTOS, RALMONY; MATTAR-ROSA, RODOLFO; YOKOTA, RODRIGO; CUNHA, TATIANA SOUSA; et al. Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1-7) and Bradykinin. JOURNAL OF DIABETES RESEARCH, v. 2015, p. 13-pg., 2015-01-01. (10/51904-9, 11/14548-2)