Inactivation of alpha1-antiproteinase (alpha1-AT) and changes in antioxidants' plasma levels in subarachnoid hemorrhage.
Recent studies have suggested that a quantitative or a qualitative imbalance between the activity of proteases and its inhibitors hypothetically might be involved in intracranial aneurysm rupture. In the present study we test the hypothesis that the systemic reduction of alpha1-antitrypsin activity might be related to the elevated oxidative potential exerted by cigarette smoking and/or to a systemic low antioxidant capacity. We studied, in a series of 57 patients bearing intracranial aneurysms, the relationship between alpha1-antitrypsin activity, cigarette smoking and the following variables measured in plasma: vitamin A, vitamin E, thiol groups, urate and lipid peroxide levels. Serum levels of alpha1-antitrypsin are higher in patients with subarachnoid hemorrhage than in cases of unruptured aneurysms, while the levels of vitamin A and vitamin E are significantly lower in patients that suffered subarachnoid hemorrhage than in controls. Both vitamin A and E levels are related to the occurrence of rupture of the aneurysm, as elicited by logistic regression analysis (P=0.017 and P=0.014, respectively), with a protective effect of higher levels of the variables, as shown by their odds ratio (0.028 and 0.84, respectively). No significant changes in the strength of the association could be appreciated when controlling for smoking habit. None of the other tested variables could be related to the occurrence of the aneurysm rupture. Both alpha1-antitrypsin serum level and the level of vitamin A appeared to be independently related to alpha1-antitrypsin collagenase inhibitory capacity percentage (P=0.03 and P=0.025), with no independent influence of the type of aneurysm and the smoking habit. The results of the present study show that the qualitative pattern of alpha1-antitrypsin is significantly related to the serum level of liposoluble vitamin A, while the type of aneurysm and the smoking habit have no independent influence. This suggests that in a situation in which systemic levels of vitamin A are reduced, the risk of a reduced activity of alpha1-antitrypsin as controller of proteases is elevated, with the consequent increased risk of aneurysm bleeding.
Paolo
G
G
Department of Neurosurgery, Istituto Clinico Humanitas, Rozzano, Milan, Italy.
Paola
G
G
y Baena Riccardo
R
R
Catherine
K
K
Vittorio
G
G
Fulvio
T
T
Barbara
B
B
Flavio
T
T
Nicoletta
F
F
Fulvio
M
M
D000704:Analysis of Variance; D000975:Antioxidants / Q000032:analysis*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000097:blood* / Q000601:surgery; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D018384:Oxidative Stress; D012907:Smoking; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000209:etiology / Q000601:surgery; D013438:Sulfhydryl Compounds / Q000097:blood; D014527:Uric Acid / Q000097:blood; D014801:Vitamin A / Q000097:blood*; D014810:Vitamin E / Q000097:blood*; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000378:metabolism*
D000975:Antioxidants; D013438:Sulfhydryl Compounds; D000515:alpha 1-Antitrypsin; D014801:Vitamin A; D014810:Vitamin E; D014527:Uric Acid