A Novel Antiapoptotic Role for α1-Antitrypsin in the Prevention of Pulmonary Emphysema

• DOI: 10.1164/rccm.200512-1842oc
• Publication Date: 2006-03-03T02:14:25Z
• Authors: Irina Petrache; Iwona Fijalkowska; Lijie Zhen; Terry R. Medler; Emile Brown; Pedro Cruz; Kang-Hyeon Choe; Laimute Tarasevic...; Robertas Scerbavi...; Lee Shapiro; Bing Zhang; Sihong Song; Dan Hicklin; Norbert F. Voelkel; Terence Flotte; Rubin M. Tuder
• Keywords: Pathogenesis; Serpin; Alpha 1-antitrypsin deficiency

Rationale: There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by destruction. The association of α1-antitrypsin deficiency with the development has supported concept protease/antiprotease imbalance mediates cigarette smoke–induced emphysema.Objectives: We propose that, addition to its antielastolytic effects, may have broader biological effects lung, preventing through inhibition cells apoptosis.Methods, Measurements, and Main Results: Transduction human via replication-deficient adeno-associated virus attenuated airspace enlargement caused vascular endothelial growth factor (VEGF) receptors SU5416 mice, model apoptosis-dependent lacking neutrophilic inflammation. overexpressed serine protease inhibitor accumulated suppressed caspase-3 activation oxidative stress lungs treated VEGF blocker or receptor-1 -2 antibodies. Similar results were obtained SU5416-treated rats given intravenously.Conclusions: Our findings suggest structural represents novel protective mechanism serpin against emphysema. Further elucidation this extend therapeutic options for reduced level loss function α1-antitrypsin.