CONTRIBUTION OF PURINERGIC SIGNALING TO VASCULAR CHANGES IN MODELS OF ACUTE KIDNEY INJURY INDUCED BY ISCHEMIA AND UREMIC TOXIN

• Grant number: 24/03801-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Jeferson Stabile
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 24/07191-0 - Investigation of the vascular inflammatory state in kidney injury models: contribution of purinergic signaling, AP.R

Abstract

Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function,resulting in a systemic inflammatory condition. A consequence of the LRA is the increaseof inflammatory molecules and uremic toxins (TU), leading to an inflammatory processin other organs, such as the heart and blood vessels. Indoxyl sulfate (IS) is a TUwhich originates from the diet and is linked to plasma proteins, making it difficultits elimination. It is related to cardiomyocyte hypertrophy, glomerular sclerosis, increased production of reactive oxygen species (ROS), in addition to contribute to the development of atherosclerosis. Purinergic signaling acts oncontrol of various physiological processes, in addition to being intrinsically linked toinflammation. Chronic activation of purinergic receptors and decreased activity of ectonucleotidases can favor an imbalance in the organism's homeostasis, which can act synergistically with the effects of AKI and, consequently, the IS. In this project, the effects of AKI and IS will be evaluated in the aorta of mice. Animals will undergo renal ischemia and reperfusion (IR) surgery and treatmentwith IS. Renal and vascular functional parameters will be evaluated, as well as markers ofinflammation and purinergic system in mouse aorta. Thus, we hope to contribute to the understanding of the cellular and molecular mechanisms involved in the participation of purinergic signaling in the vascular changes observed in the setting ofAKI induced by ischemia and IS uremic toxin.