The amounts of alpha 1 antitrypsin protein are reduced in the vascular wall of the acutely dissected human ascending aorta☆

BACKGROUND: Aneurysm and dissection of the ascending aorta carry the risk of life-threatening complications. The anti-protease alpha 1 antitrypsin plays an important role in the tissue protease - anti-protease equilibrium. We aim to investigate the molecular pathology of these diseases by differential proteomics and mass-spectrometric analysis. METHODS: From ascending aortic wall specimens of aneurysms, acute dissections and controls, protein amounts were analysed by the differential in-gel electrophoresis (DIGE). Significantly, different spots underwent qualitative analysis by nanospray mass spectrometry. RESULTS: Among the most significant differentially expressed protein spots in the DIGE analysis, the most notable protein identified by nanospray mass spectrometry was alpha 1 antitrypsin. This was significantly reduced in aneurysms and aortic dissections compared with controls (p<0.05). Western blot analysis confirmed the reduced amounts of alpha 1 antitrypsin in aortic dissections (p=0.008 vs controls) but not for aneurysms (p=0.258). By quantitative reverse transcription polymerase chain reaction (RT-PCR), mRNA level of alpha 1 antitrypsin was found to be increased in aortic dissections (p=0.035 vs controls), whereas in aneurysms a non-significant reduction of alpha 1 antitrypsin mRNA was present (p=0.123 vs controls). CONCLUSION: In the vascular wall of ascending aortic dissections, alpha 1 antitrypsin protein amounts are reduced compared with healthy aortas. Local alpha 1 antitrypsin deficiency in the human ascending aorta might lead to proteolytic damage easing aortic dissection.