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Interactions of kallikrein kinin system and vascular endothelial growth factor (VEGF) in animal models of intermittent hypoxia

Grant number: 12/02123-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2012
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Jair Ribeiro Chagas
Grantee:Bruna Visniauskas
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Low levels of oxygen in tissues (hypoxia) occur in a number of pathophysiological conditions, such as tumors growth, heart disease and obstructive sleep apnea syndrome (OSA). A major physiological or pathological outcome of hypoxia is to stimulate the growth of blood vessels, a process known as angiogenesis. The formation of new blood vessels is essential to the myocardium to provide oxygen and nutrients to sustain cellular metabolism. In the intermittent hypoxia (IH), an experimental model that reproduces several conditions of OSA, angiogenesis occurs, although the mechanism is not yet elucidated. In other models of hypoxia and ischemia/reperfusion, it was demonstrated a strong interaction between the vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) and its cardioprotective effects. In this project, we intend to contribute to the understanding of angiogenesis in an in vivo model of IH, studying the interactions of the KKS with VEGF in the heart. Wilde type and bradykinin B2-receptor knockouts strains of mice C57/BL6J will be exposed to events of hypoxia during a preconditioning period and then to IH during five weeks. At the end of each week the miocardium will be evaluated to verify in vivo angiogenesis, gene and protein expression of VEGF and its receptor, the components of KKS (bradykinin receptors, activity of proteases and kinins),the signaling pathways PI3K/AKT/eNOS and Src/Ras/Raf/MEK/iNOS.

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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)
VISNIAUSKAS, BRUNA; PERRY, JULIANA C.; GOMES, GUIOMAR N.; NOGUEIRA-PEDRO, AMANDA; PAREDES-GAMERO, EDGAR J.; TUFIK, SERGIO; CHAGAS, JAIR R. Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart. PHYSIOLOGICAL REPORTS, v. 9, n. 9 MAY 2021. Web of Science Citations: 0.
VISNIAUSKAS, BRUNA; SIMOES, PRISCILA S. R.; DALIO, FERNANDA M.; NAFFAH-MAZZACORATTI, MARIA D. G.; OLIVEIRA, VITOR; TUFIK, SERGIO; CHAGAS, JAIR R. Sleep deprivation changes thimet oligopeptidase (THOP1) expression and activity in rat brain. HELIYON, v. 5, n. 11 NOV 2019. Web of Science Citations: 0.

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