Evaluation of blood pressure and changes in the renin-angiotensin system in an animal model of sickle cell anemia

• Grant number: 17/03954-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Nicola Amanda Conran Zorzetto
• Grantee: Pamela Lara de Brito
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

Sickle cell anemia (SCA) is a hereditary hematological disease that affects the ²-globin gene. The disease is caused by a single base substitution of an adenine for a thymine in the gene, leading to the synthesis of anomalous hemoglobin S (HbS). At low oxygen concentrations, HbS polymerizes and the erythrocyte adopts a characteristically sickled shape. These red cells display altered physico-chemical properties and therefore interact with the endothelium, platelets and leukocytes; together with hemolytic processes, these interactions may result in the vascular inflammation which is associated with disease and eventually vaso-occlusive processes. The constant sickling of red blood cells and vaso-occlusive processes in the renal medulla can lead to the obstruction of blood flow in the vessels and renal ischemia. A major clinical complication of SCA is renal dysfunction, which presents high morbidity and mortality. The Renin-Angiotensin System (RAS) regulates the formation of Angiotensin II (Ang II) in response to hemodynamic changes, in turn promoting vasoconstriction and fluid balance, aiming to normalize blood pressure (BP). The only drug currently FDA approved as therapy for SCA is Hydroxyurea (HU), which reduces vaso-occlusive events and has immediate anti-inflammatory effects. Our preliminary results demonstrate that young mice with SCA have reduced BP, alterations in the distribution of the Ang II type 2 receptor (ATR2), Angiotensin converting enzyme (ACE) and rennin, as compared to control mice. The purpose of this study was to investigate whether there is a correlation between BP and changes in RAS and renal changes in an animal model of SCA and to compare these parameters in young mice and older mice. Additionally, we will evaluate the effects of 4 weeks of treatment with HU or an ACE inhibitor (ACEi; used in patients with AF who have albuminuria and proteinuria and to prevent nephrological disorders and chronic kidney disease) on these parameters. We hope that data obtained will improve our understanding of how renal changes may contribute to hemodynamic changes in SCA and possible means to limit these changes. (AU)

Scientific publications

(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)

BRITO, PAMELA L.; DOS SANTOS, ALISSON F.; CHWEIH, HANAN; FAVERO, MARIA E.; GOTARDO, ERICA M. F.; SILVA, JULIETE A. F.; LEONARDO, FLAVIA C.; FRANCO-PENTEADO, CARLA F.; DE OLIVEIRA, MARIANA G.; FERREIRA JR, WILSON A.; et al. Reduced blood pressure in sickle cell disease is associated with decreased angiotensin converting enzyme (ACE) activity and is not modulated by ACE inhibition. PLoS One, v. 17, n. 2, p. 19-pg., 2022-02-03. (17/03954-6, 14/00984-3, 15/04485-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BRITO, Pamela Lara de. Evaluation of blood pressure and changes in the renin-angiotensin system in an animal model of sickle cell anemia. 2019. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.