| First Author | Hume PS | Year | 2022 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 323 |
| Issue | 4 | Pages | L391-L399 |
| PubMed ID | 35943156 | Mgi Jnum | J:330028 |
| Mgi Id | MGI:7355167 | Doi | 10.1152/ajplung.00491.2021 |
| Citation | Hume PS, et al. (2022) Cigarette smoke-induced airspace disease in mice develops independently of HIF-1alpha signaling in leukocytes. Am J Physiol Lung Cell Mol Physiol 323(4):L391-L399 |
| abstractText | The pathogenesis of chronic obstructive pulmonary disease (COPD), a prevalent disease primarily caused by cigarette smoke exposure, is incompletely elucidated. Studies in humans and mice have suggested that hypoxia-inducible factor-1alpha (HIF-1alpha) may play a role. Reduced lung levels of HIF-1alpha are associated with decreased vascular density, whereas increased leukocyte HIF-1alpha may be responsible for increased inflammation. To elucidate the specific role of leukocyte HIF-1alpha in COPD, we exposed transgenic mice with conditional deletion or overexpression of HIF-1alpha in leukocytes to cigarette smoke for 7 mo. Outcomes included pulmonary physiology, aerated lung volumes via microcomputed tomography, lung morphometry and histology, and cardiopulmonary hemodynamics. On aggregate, cigarette smoke increased the aerated lung volume, quasi-static lung compliance, inspiratory capacity of all strains while reducing the total alveolar septal volume. Independent of smoke exposure, mice with leukocyte-specific HIF-1alpha overexpression had increased quasi-static compliance, inspiratory capacity, and alveolar septal volume compared with mice with leukocyte-specific HIF-1alpha deletion. However, the overall development of cigarette smoke-induced lung disease did not vary relative to control mice for either of the conditional strains. This suggests that the development of murine cigarette smoke-induced airspace disease occurs independently of leukocyte HIF-1alpha signaling. |
