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Evaluation of the participation of aryl hydrocarbon receptor (AhR) on endothelial dysfunction on mice fed with hyperlipidic diet: a role of renin angiotensin system (RAS))

Grant number: 18/21199-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: January 01, 2019
End date: December 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Juliana de Andrade Bolsoni
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Overweight is a risk factor for many comorbidities, like cardiovascular diseases. In obesity, there's an imbalance on the production and actions of vasoactive molecules, compromising the vascular function. Literature shows that, in obesity, oxide nitric synthesis is reduced, usually associated with inhibition of eNOS or with the increased production of reactive oxygen species. Furthermore, obese individuals are more likely to develop hypertension, and the activation of the renin angiotensin system (RAS) is one of the mechanism that justify this interaction. Studies have shown that obese individuals have an inadequate suppression of RAS, leading to endothelium dysfunction and hypertension, common in obesity. Moreover, studies have shown that knockout animals for AhR have hypotension due to a less activated RAS, improving vascular reactivity and blood pressure regulation on those animals. In this context, AhR may have an important role on vascular function, influencing the vasomotor response. Therefore, our Project proposes to investigate if endothelial dysfunction due to obesity in mice is related with the activation of RAS by activation of AhR. Our hypothesis is that the absence of AhR, in knockout obese animals, will protect aortic function due to a decreased activation of RAS. This study will allow us to better understand the relation between obesity and cardiovascular diseases.

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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)
DA SILVA, JOSIANE FERNANDES; BOLSONI, JULIANA A.; DA COSTA, RAFAEL M.; ALVES, JULIANO, V; BRESSAN, ALECSANDER F. M.; SILVA, LUIZ EDUARDO, V; COSTA, TIAGO J.; OLIVEIRA, ANTONIO E. R.; MANZATO, CARLA P.; AGUIAR, CARLOS A.; et al. Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction. British Journal of Pharmacology, v. 179, n. 12, p. 15-pg., . (18/21199-3, 13/08216-2, 19/22579-7, 16/16207-1)