Therapeutic benefit of purinergic manipulation in the carotid body of heart failure rats.

• Grant number: 25/04634-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Davi José de Almeida Moraes
• Grantee: Adelson Héric Alves Monteiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06886-7 - Role of purinergic receptors in the carotid body in heart failure, AP.JP2

Abstract

The carotid bodies (CBs) are small organs located at the bifurcation of the common carotid artery, acting as multimodal sensors that monitor blood gases and substances such as insulin and glucose. Their stimulation triggers autonomic reflexes, including bronchoconstriction, hyperventilation, and increases in blood pressure. CBs contain glomus cells (type I), involved in sensory responses, and sustentacular glial cells (type II), which appear to have a supportive function. In heart failure (HF), CBs become hyperactive, contributing to disease progression. The resection of these organs has been used to treat respiratory diseases and HF by reducing sympathetic activity and improving cardiac function. However, bilateral removal may lead to adverse events, such as prolonged sleep apnea. Thus, an alternative strategy is genetic manipulation to modulate their activity without compromising their physiological functions. Recently, technical advances have enabled viral gene transfer into the CBs of rats, opening new therapeutic possibilities. This research project proposes to reduce the purinergic signaling in CBs by using viral vectors to express a protein that blocks exocytosis in glial cells and an enzyme that degrades ATP, minimizing aberrant transmission. HF rats will be used, subjected to viral vector injection into the CBs, and monitored for six weeks. The evaluation will include echocardiography, heart rate measurement, respiratory function tests, and histological analysis of the organs. It is expected that this approach will allow modulation of CBs function, reducing the deleterious effects of sympathetic hyperactivity without compromising physiological homeostasis. (AU)