Study of prevention of acute lung injury and ACE2 metabolism in experimental model of pulmonary transplantation

• Grant number: 22/07610-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: January 31, 2025
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Paulo Manuel Pêgo-Fernandes
• Grantee: Paulo Manuel Pêgo-Fernandes
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Karina Andrighetti de Oliveira Braga

Abstract

Lung transplantation (LTx) is a therapeutic option established worldwide for end-stage lung diseases. However, as most donors evolve with brain death, the donated lung may have undergone perfusion changes, followed by an increase in the production of pro-inflammatory factors that favor the induction of acute lung injury (ALI). These factors could increase the incidence of primary graft dysfunction (PGD) after LTx. In this sense, in view of the angiotensin-converting enzyme 2 (ACE2) expression throughout the lung territory, its role in the regulation of several fibrotic, inflammatory and oxidative processes and the use of ACE2 activators in the regulation of pulmonary pathological processes, the present project aims to study the hypothesis that the activation of ACE2 by diminazene aceturate (DIZE) prevents the establishment of ALI associated with LTx. To evaluate the effect of ACE2 activation on the prevention of ALI associated with LTx, the left unilateral transplant will be performed in recipient animals. Therefore, the animals will be randomly distributed in the following experimental groups: sham, brain death (BD) and DIZE. The last two groups will undergo the brain death process, treated with saline solution (0.9%) or DIZE (15 mg / kg-1) and kept on mechanical ventilation for 6 hours (donor). After this period, cardiopulmonary block extraction and left unilateral transplantation will be performed, followed by reperfusion for 2 hours (recipient). Hemodynamic, gasometric, pulmonary mechanics, inflammatory and oxidative parameters will be evaluated in samples collected from donors and recipients. The results will be presented as mean ± standard error of the mean (E.P.M.) and will be treated for verification of significance (p <0.05). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA-MELO, PAOLO; NEPOMUCENO, NATALIA APARECIDA; RUIZ, LILIANE MOREIRA; CORREIA, ARISTIDES TADEU; VILELA, VANESSA SANA; BRAGA, KARINA ANDRIGHETTI DE OLIVEIRA; MANZUTI, GIOVANA MARIA; FEITOSA, DEYMISSON DAMITENE MARTINS; KENNEDY-FEITOSA, EMANUEL; WANG, AIZHOU; et al. Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation. SCIENTIFIC REPORTS, v. 14, n. 1, p. 12-pg., 2024-10-09. (22/07610-8)