Potential cardioprotective role of angiotensin II receptor type 2 (AT2) in aging-associated cardiac senescence: possible involvement of inflammasomes

• Grant number: 22/00057-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Maria Luiza de Morais Barreto de Chaves
• Grantee: Larissa Maria Zacarias Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/17031-2 - Inflammasome in the cardiac physiopathology, AP.TEM

Abstract

The heart is subject to numerous pathophysiological stimuli, which can lead to the development of cardiovascular diseases. Aging is one of the risk factors for these diseases, with the activation of inflammatory cascades and protein complexes called inflammasomes, in addition to the synthesis and release of cytokines. Furthermore, there is the production of reactive oxygen species and activation of senescence pathways, which lead to structural and functional changes in the heart. One of the systems that act directly on cardiac function and morphology is the renin-angiotensin system (RAS). This main effector is Ang II, which, when binding to AT1 and AT2 receptors, mostly performs antagonistic responses. Thus, hypertrophic and inflammatory responses are associated with AT1 and cardioprotective responses with AT2. The hypothesis of the present study is that the AT2 receptor exerts cardioprotective effects on aging and that its suppression triggers the activation of inflammatory processes, with the activation of inflammasomes, which contributes to the inflammatory phenotype associated with aging. To test it, we will use wild mice (WT C57BL/6) or knockouts for the AT2 receptor, with 3 months (young) or 18 months of age (elderly). As experimental strategies, analyzes of gene and protein expression of cardiac senescence markers, histological analyzes and analysis of cardiac function will be carried out. Finally, the contribution of the inflammasome in the context of aging will be evaluated, through the analysis of the production of inflammatory cytokines and the activity of caspase. (AU)

Academic Publications

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

RODRIGUES, Larissa Maria Zacarias. Potential cardioprotective role of Type 2 Angiotensin II Receptor (AT2) in aging-associated to cardiac senescence: possible involvement of inflammasomes.. 2024. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.