Analysis of alterations in renin-angiotensin and kallikrein-kinin systems in Pediatric Obesity and its contribution to associated complications

• Grant number: 18/16653-7
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): December 01, 2018
• Status: Discontinued
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal researcher: Dulce Elena Casarini
• Grantee: Nayara Azinheira Nobrega Cruz
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 19/09745-5 - The use of a human-derived placental unit model to study the role of the kinin-kallikrein system on placental endothelial-trophoblast interactions and angiogenesis, BE.EP.DD

Abstract

The occurrence of overweight and Obesity among Brazilian children and youth has increased in the last decades and generates concern. The Obesity has become a public health problem around the globe, once it is a risk factor to related diseases such as, Hypertension, Dyslipidaemias and insulin resistance, which together composes a metabolic syndrome diagnosis. Obesity has also a social, psychological and economic impact. There are evidences that the RAS has a role in the physiopathology of several diseases, as example, Diabetes, Alzheimer, metabolic syndrome and Obesity, besides its well establish contribution to the development and sustain of hypertension. The RAS is actually more than a simple cascade constituted of a protein precursor, angiotensinogen, two proteases, renin and ACE and an effector peptide, Ang II. The discovery of new axis of the system as, ACE2/Ang 1-7/Mas and Ang A/Alamandine/MrgD which present peptides with similar or opposite functions to Ang II highlight a complex balance of the system, once there is counter regulatory axis to ensure the organism homeostasis. Additionally, there is an important crosstalk between RAS and KKS and RAS and SNS, both critical to organic functions. Previous results from our group have showed that the RAS and KKS are modulated in Obesity. There is a positive correlation between diminished levels of the vasodilators peptides, BK and Ang 1-7, and the increase of body weight. Also, increased concentrations of Ang I and desArg9BK, an inflammatory kinin, were found in obese youth. Therefore; this study aims to quantify the peptides of RAS and KKS in children and adolescents aged from 6 to 19 years, whose are enrolled to the social programme Estação Conhecimento and or public schools of Vitória-ES. Also, evaluate the expression and activity of the main enzymes responsible by generate or inactivate the peptides of RAS and KKS, in special ACE and ACE2, that are relevant interaction points between the two systems. Thus, elucidate the roles of RAS and KKS in the physiopathology of Obesity towards to development of new strategies for prognostic and therapeutics. (AU)