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).


CONCLUSIONS
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.
Schachner
Thomas
T
Department of Cardiac Surgery, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Thomas.Schachner@i-med.ac.at
Golderer
Georg
G
Sarg
Bettina
B
Lindner
Herbert H
HH
Bonaros
Nikolaos
N
Mikuz
Gregor
G
Laufer
Guenther
G
Werner
Ernst R
ER
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000784:Aortic Dissection / Q000209:etiology* / Q000378:metabolism; D001014:Aortic Aneurysm / Q000209:etiology* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism
D000515:alpha 1-Antitrypsin