Sex differences in the lung ACE/ACE2 balance in hypertensive rats

Author(s):Show less -

Martins, Flavia L. ^[1] ; Tavares, Caio A. M. ^[2] ; Malagrino, Pamella A. ^[1] ; Rentz, Thiago ^[1] ; Benetti, Acaris ^[1] ; Rios, Thiago M. S. ^[1] ; Pereira, Gabriel M. D. ^[1] ; Caramelli, Bruno ^[3] ; Teixeira, Samantha K. ^[1] ; Krieger, Jose E. ^[1] ; Girardi, Adriana C. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Lab Genet & Mol Cardiol, Heart Inst InCor, Med Sch, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Cardiogeriatr Unit, Heart Inst InCor, Med Sch, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Cardiol Interdisciplinary Med Unit, Heart Inst InCor, Med Sch, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: BIOSCIENCE REPORTS; v. 41, n. 12 DEC 2021.
• Web of Science Citations: 0

Abstract

The angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II) and angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7)) pathways are coexpressed in most tissues. The balance between these pathways determines, at least in part, whether tissue damage will occur in response to pathological stimuli. The present study tested the hypothesis that male sex and high blood pressure are associated with ACE/ACE2 imbalance in the lungs. Experiments were conducted in male and female Wistar rats and spontaneously hypertensive rats (SHRs). Lung ACE and ACE2 gene expression was also evaluated in normotensive and hypertensive humans using the Genotype-Tissue Expression (GTEx) project. Compared with Wistar rats and female SHRs, male SHRs displayed reduced lung ACE2 mRNA, ACE2 protein abundance and ACE2 activity, and increased Ang II concentration. Lung ACE mRNA levels were higher in male SHRs than in Wistar rats, whereas lung ACE protein abundance and activity were similar among the four groups of rats. Lung Ang-(1-7) concentration was higher in female than in male SHRs (89 +/- 17 vs. 43 +/- 2 pg/g, P<0.05). Lung ACE to ACE2 mRNA expression in hypertensive patients was significantly higher than that in normotensive subjects. Taken together, these results demonstrate that male hypertensive rats display imbalance between the ACE/Ang II and ACE2/Ang-(1-7) pathways in the lungs mainly attributable to ACE2 down-regulation. Further studies should be conducted to investigate whether this imbalance between ACE/ACE2 may promote and accelerate lung injury in respiratory infections, including coronavirus disease 2019 (COVID-19). (AU)

• FAPESP's process: 20/05338-3 - Modulation of ACE2 in experimental hypertension and in response to treatment with ACE inhibitors and ARBs: potential implications for COVID-19 severity and therapeutic targets
• Grantee: Adriana Castello Costa Girardi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/22140-7 - Molecular bases of renal tubular function and dysfunction
• Grantee: Adriana Castello Costa Girardi
• Support Opportunities: Research Projects - Thematic Grants