Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation

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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 ; Cypel, Marcelo ; Fernandes, Paulo Manuel Pego

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 14, n. 1, p. 12-pg., 2024-10-09.

Abstract

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-alpha (p = 0.02), IL-6 (p = 0.001), IL-1 beta (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx. (AU)

• FAPESP's process: 22/07610-8 - Study of prevention of acute lung injury and ACE2 metabolism in experimental model of pulmonary transplantation
• Grantee: Paulo Manuel Pêgo-Fernandes
• Support Opportunities: Regular Research Grants