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ANGIOEDEMA INDUCTION IN RATS OVEREXPRESSING THE B2 KININ RECEPTOR: AN ALTERNATIVE ANIMAL MODEL FOR HEREDITARY ANGIOEDEMA STUDY

Grant number: 16/23304-3
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 05, 2017
Effective date (End): March 04, 2018
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:João Bosco Pesquero
Grantee:Camila Lopes Veronez
Supervisor: Michael Bader
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Research place: Max Planck Society, Berlin, Germany  
Associated to the scholarship:15/25494-1 - Development of a gene therapy model for hereditary angioedema based on SERPING1 gene edition by CRISPR-Cas9 system, BP.PD

Abstract

Hereditary angioedema (HAE) is mainly known as an autosomal dominant disease characterized by C1 esterase inhibitor (C1-INH) deficiency. C1-INH inhibits proteases of the complement pathways, coagulation factors XI (FXI) and XII (FXII), plasma kallikrein (KK), and its deficiency results in an uncontrolled release of bradykinin (BK), which binds to the kinin B2 receptor (B2R) leading to inflammation and vasodilatation. Considering that the C1-INH-deficiency mice described do not show phenotypic abnormalities but increased vascular permeability, we developed an alternative HAE animal model. Transgenic rats overexpressing the B2R in the endothelium (VECDH-B2R) were successfully generated and preliminary analysis indicates an exacerbated response to BK stimuli. Our objective in this one-year project is to challenge the VECDH-B2R rats to develop angioedema through angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPPIV) inhibitors treatment, with local irritants able to induce plasma leakage and local inflammation as mustard oil, and with estrogen therapy, once these ones correspond to known triggering factors in human HAE. Edema formation will be analyzed by means of vascular permeability increasing with Evans blue tracer. Plasma Kallikrein-Kinin System (KKS) proteins activation will be monitored by Western Blotting and qPCR in different tissues.

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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)
VERONEZ, CAMILA LOPES; MAGHSODI, SARA; TODIRAS, MIHAIL; POPOVA, ELENA; RODRIGUES, ANDRE FELIPE; QADRI, FATIMUNNISA; PESQUERO, JOAO BOSCO; BADER, MICHAEL. Endothelial B2-receptor overexpression as an alternative animal model for hereditary angioedema. ALLERGY, v. 74, n. 10, . (14/27198-8, 16/23304-3)

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