Alpha-1-Antitrypsin Deficiency in Aneurysmal Disease

Abstract

α₁-Antitrypsin (α₁-AT) deficiency may play a role in arterial aneurysmal disease by allowing increased proteolysis of arterial structural proteins. α₁-AT levels are influenced by variation at the PI (protease inhibitor) locus. PI phenotypes were determined in 173 patients with abdominal aortic aneurysms (77 from Pitsburgh, 96 from London) and in 72 patients with intracranial aneurysms (26 from Pittsburgh, 46 from London). No excess of PI deficiency alleles was observed in either of the aortic aneurysm data sets or in the Pittsburgh intracranial aneurysm data. The PPZ deficiency allele frequency in the London intracranial aneurysm data was 8-fold higher than in controls; however, this was not significant after correcting for multiple comparisons. PI phenotype had no effect on aneurysm age-at-diagnosis within any of the data sets. Smoking history had an effect on aneurysm age-at-diagnosis only within the Pittsburgh intracranial-aneurysm data.

Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity

“…There should be a theoretical association between aortic aneurismal disease and AAT deficiency due to uninhibited Significance was obtained by v 2 (3 · 3 table) as the alleles were distributed unevenly between the three cohorts (P = 0.0000001) Significance was obtained by v 2 (3 · 3 Table) for the MZ genotype which was distributed unevenly between the three cohorts (P = 0.0000001) elastase activity on the elastic tissue of arterial walls, but this has not been supported in published data nor has an association been shown with intracranial aneurysms (St Jean et al 1996;Needham and Stockley 2004). However, elastin is a major component of vessel wall elastic lamina, and degradation of elastic fibbers may be important in the lowering of blood pressure, which is a well-known risk factor for CVD and AMI.…”

Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve

“…In addition, a1AT may play an important role in maintaining the integrity of connective tissue, including the blood vessel wall. Aneurysmal pathogenesis appears to be complex, and several investigators have tried to find a connection between a1AT deficiency and formation of abdominal aortic aneurysms [16,25,26]. Deficiency of a1AT may theoretically affect the arterial wall by disturbing the balance between proteases and their inhibitors.…”

American Thoracic Society/European Respiratory Society: Standards in Diagnostik und Therapie bei Patienten mit Alpha-1-Antitrypsin-Mangel

“…Dazu gehören die systemische Vaskulitis, wie die ANCA-positive Wegener's Granulomatose und die nekrotisierende Panniculitis [149 ± 152], die periphere Neuropathie [153] sowie cerebrale und periphere arterielle Aneurysmen [154]. Letztere konnten in gröûeren Studien nicht bestätigt werden [155]. Einige berichten eine Verschlechterung der Vaskulitis-Symptome durch á 1 -Antiproteinase-Behandlung [149,156].…”