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

Abstract

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.

• Authors: Thomas Schachner, Georg Golderer, Bettina Sarg, Herbert H Lindner, Nikolaos Bonaros, Gregor Mikuz, Guenther Laufer, Ernst R Werner
• Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (Eur J Cardiothorac Surg) Vol. 37 Issue 3 Pg. 684-90 (Mar 2010) ISSN: 1873-734X [Electronic] Germany
• PMID: 19709897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Chemical References

• alpha 1-Antitrypsin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Aortic Dissection (etiology, metabolism)
• Aortic Aneurysm (etiology, metabolism)
• Electrophoresis, Gel, Two-Dimensional (methods)
• Electrophoresis, Polyacrylamide Gel (methods)
• Female
• Humans
• Male
• Mass Spectrometry (methods)
• Middle Aged
• Molecular Sequence Data
• Proteomics (methods)
• Young Adult
• alpha 1-Antitrypsin (genetics, metabolism)
• alpha 1-Antitrypsin Deficiency (complications, diagnosis, metabolism)