Evaluation of ectonucleotidases activity and purine levels in mouse aortas in response to acute kidney injury (AKI) due to renal ischemia and reperfusion

• Grant number: 23/16802-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2024
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Cristina Ribas Fürstenau
• Grantee: Ana Carolina da Costa Peres
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Cardiorenal syndrome (CRS) is a condition related to kidney and heart dysfunction. This syndrome is classified in five types: types 1 and 2 being cardiorenal syndromes where, respectively, an acute and chronic cardiac injury lead to renal dysfunction; types 3 and 4 are renocardial syndromes, in which, respectively, acute and chronic kidney damage lead to cardiac dysfunction; and, the fifth type consists of cardiac and renal dysfunction originating from a systemic condition. Type 3 CRS is therefore described by acute kidney injury (AKI) and can be confirmed by pro- and anti-inflammatory markers. AKI can originate in different situations, such as ischemia and reperfusion that occur in kidney transplant situations, for example. Besides the kidneys, AKI can also affect the heart (SCR3) and blood vessels through hemodynamic, neurohumoral, mechanical, biochemical and other factors. The purinergic system is a cellular communication system that acts in situations of inflammation and can modulate it through its effectors, nucleotides and nucleosides, mainly ATP, ADP and adenosine. Signaling through nucleotides and nucleosides plays an important role in the regulation of the vascular system, influencing both the reactivity of vessels (contraction and relaxation), their structure (cell growth and regulation), and cellular inflammatory processes, which can impact the SCRs of all types. In addition to ATP being well described as an energy currency, it is also an extracellular signal that acts in situations of inflammation. Its effects are mediated by binding to specific receptors on the cell membrane named purinergic receptors. Ectonucleotidases, in turn, are enzymes that hydrolyze nucleotides, breaking the phosphate group present in these molecules, thus ending nucleotide signaling and allowing nucleoside signaling to begin. These enzymes are divided into four gene families, which encompass ecto-nucleotide pyrophosphate/phosphodiesterases (ENPPs), alkaline phosphatases, ecto-nucleoside triphosphate diphosphohydrolases (ENTPDases) and 5'-nucleotidase. The enzymes NTPDases1 and 2 and ecto-5'-nucleotidase are particularly present in blood vessels and allow homeostatic integration and control of inflammatory vascular reactions and immune cells at sites of injury when expressed in endothelial or immune cells. Furthermore, they play an important role in the generation of adenosine, which, mediated by P1 purinergic receptors, acts in regulating inflammatory responses and limiting the destruction of inflammed tissue.