| First Author | Abadir P | Year | 2024 |
| Journal | Biochem Pharmacol | Volume | 220 |
| Pages | 115978 | PubMed ID | 38081369 |
| Mgi Jnum | J:353505 | Mgi Id | MGI:7573801 |
| Doi | 10.1016/j.bcp.2023.115978 | Citation | Abadir P, et al. (2023) Unlocking the protective potential of the angiotensin type 2 receptor (AT(2)R) in acute lung injury and age-related pulmonary dysfunction. Biochem Pharmacol 220:115978 |
| abstractText | Despite its known importance in the cardiovascular system, the specific role and impact of the angiotensin type 2 receptor (AT(2)R) in lung physiology and pathophysiology remain largely elusive. In this study, we highlight the distinct and specialized lung-specific roles of AT(2)R, primarily localized to an alveolar fibroblast subpopulation, in contrast to the angiotensin type 1 receptor (AT(1)R), which is almost exclusively expressed in lung pericytes. Evidence from our research demonstrates that the disruption of AT(2)R (AT(2)R(-/y)), is associated with a surge in oxidative stress and impaired lung permeability, which were further intensified by Hyperoxic Acute Lung Injury (HALI). With aging, AT(2)R(-/y) mice show an increase in oxidative stress, premature enlargement of airspaces, as well as increased mortality when exposed to hyperoxia as compared to age-matched WT mice. Our investigation into Losartan, an AT(1)R blocker, suggests that its primary HALI lung-protective effects are channeled through AT(2)R, as its protective benefits are absent in AT(2)R(-/y) mice. Importantly, a non-peptide AT(2)R agonist, Compound 21 (C21), successfully reverses lung oxidative stress and TGFbeta activation in wild-type (WT) mice exposed to HALI. These findings suggest a possible paradigm shift in the therapeutic approach for lung injury and age-associated pulmonary dysfunction, from targeting AT(1)R with angiotensin receptor blockers (ARBs) towards boosting the protective function of AT(2)R. |
