Investigation of the vascular inflammatory state in kidney injury models: contribution of purinergic signaling

• Grant number: 24/07191-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Cristina Ribas Fürstenau
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• Associated researchers: Marcela Sorelli Carneiro Ramos
• Associated scholarship(s): 24/03801-9 - CONTRIBUTION OF PURINERGIC SIGNALING TO VASCULAR CHANGES IN MODELS OF ACUTE KIDNEY INJURY INDUCED BY ISCHEMIA AND UREMIC TOXIN, BP.DR; 24/03888-7 - Investigation of the vascular inflammatory state in models of acute kidney injury: effect of P-cresyl sulfate on purinergic signaling, BP.MS; 24/15026-0 - Evaluation of gene expression of ectonucleotidases and purinergic receptors in the aorta of mice submitted to acute kidney injury (AKI) due to ischemia and uremic toxin, BP.IC; 24/17670-3 - Expression Profile of Purinergic Receptors and Ectonucleotidases in Vascular Cell Lines, BP.IC

Abstract

Acute kidney injury (AKI) is characterized by a sudden reduction in kidney function that persists for less than three months, with morbidity and mortality rates greatly increasing. Ischemia and reperfusion (IR) and/ or accumulation of uremic toxins (UT) may cause AKI. Inflammation plays a crucial role in the pathophysiology of AKI through the activation of resident immune cells, releasing inflammatory cytokines (IL-6, IL-1² e IL-18) and TNF-±, and the recruitment of peripheral leukocytes, exacerbating the injury. AKI can also affect distant organs, such as vascular beds far from the kidney, by releasing soluble molecules. Purinergic signaling is performed by extracellular nucleotides and nucleosides which activate specific purinergic receptors and are hydrolyzed by ectonucleotidases. In the vasculature, nucleotide signaling influences vasomotor responses and vascular inflammation, since ATP can act as a pro-inflammatory molecule and adenosine as an anti-inflammatory molecule. This study aims to elucidate the inflammatory state of the aorta of mice subjected to IR and TU AKI models, emphasizing the contribution of purinergic signaling. In the aortas of mice subjected to AKI models, the following will be investigated: 1) the activation and recruitment of cells of the local innate immune system; 2) the expression of local and circulating cytokines, enzymes associated with the production of reactive oxygen species (ROS), and receptors and enzymes of the purinergic system; 3) histological changes in the composition of the intima, media and adventitia layers of the vessel; and 4) vascular contraction and relaxation responses. It is expected to prove that the aorta is inflamed and its reactivity is altered as a result of AKI partially caused by an impairment in the expression and functioning of purinergic signaling components, which may direct new diagnostic and therapeutic approaches. (AU)