Interaction between the Alamandina/MrgD axis and the NLRP3 inflammasome in cardiac hypertrophy

• Grant number: 25/07646-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Luiza de Morais Barreto de Chaves
• Grantee: Gabriela Cavazza Cerri
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with cardiac hypertrophy (CH) being an important risk factor that precedes heart failure. Alamandine, via MrgD, has shown promise as a peptide that improves cardiovascular function and attenuates the process of CH. The NLRP3 inflammasome is an intracellular receptor associated with innate immunity and a key mediator of inflammation, which has been linked to the progression of CVDs. Evidence suggests that alamandine has the potential to negatively modulate NLRP3 activation; however, this interaction has not yet been investigated, particularly in the cardiovascular context. Given the importance of the MrgD receptor and the NLRP3 inflammasome for cardiovascular function, as well as the potential for interaction between these components, this project aims to investigate the role of the alamandine/MrgD axis in the regulation of NLRP3 in isoproterenol-induced cardiomyocyte hypertrophy, a synthetic beta-adrenergic agonist. The hypothesis to be tested in this study is that the alamandine/MrgD axis acts as a cardioprotective agent in the classical beta-agonist-induced cardiac hypertrophy model and that this action occurs, at least in part, mediated by the NLRP3 inflammasome. To test this hypothesis, the project will focus primarily on in vivo experiments using C57BL/6 and NLRP3-KO mice, complemented by in vitro studies with the AC16 cell line. Experimental approaches such as western blotting and PCR will be employed to assess the activity and expression of NLRP3 components and MrgD under different conditions of stimulation and inhibition, as well as in response to hypertrophic challenge. Cardiac function will be evaluated by echocardiography and arterial blood pressure will be evaluated by tail-cuff plethysmography. This study aims to fill a significant gap in literature and provide new insights into molecular mechanisms and potential therapeutic targets for the treatment of cardiovascular diseases.