Does alpha-1-proteinase inhibitor play a protective role in coronary atherosclerosis?
BACKGROUND
alpha-1-proteinase inhibitor (alpha-1-PI) might appear to be actively involved in atherogenesis as an important regulator protecting elastic tissue from damage by proteinases as well as lipid accumulation in arterial wall.


METHODS
alpha-1-PI genetic variants were examined in 156 male coronary atherosclerosis patients (mean age 49+/-9 years). The frequency of alpha-1-PI phenotypes was determined in 1577 healthy individuals. Also, 108 long-survivors (mean age 92.7+/-4.3 years) were investigated for alpha-1-PI phenotype. The serum level of alpha-1-PI was examined in 43 coronary atherosclerosis patients (mean of age 49.6+/-8.1 years) and in different age groups of healthy males. A correlations between seruma-1-PI concentration and apoB, and apoA-1 were calculated. Relationship between serum alpha-1-PI and apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio was determined. Isoelectric focusing of alpha-1-PI phenotypes was performed on thick polyacrylamide gels with ampholytes pH 3.5-5.0, 4.5-6.5 and 4.2-5.0. A quantitative assessment of alpha-1-PI, apoB and apoA-1 was performed by ELISA method using antibodies against human alpha-1-PI, apoB and apoA-1.


RESULTS
The phenotype PI ZZ of alpha-1-PI associated with a severe congenital deficiency of alpha-1-PI in patients and long-lived subjects was not found. In population this phenotype (0.06%) as well as PI SS phenotype (0.06%) was detected once. No significant difference was found in the frequency of PI*M, PI*S and PI*Z genes in the coronary atherosclerosis group and population. The PI*Z gene was significantly more frequent in patients with coronary atherosclerosis than in long-survivors (P<0.01). The correlation between blood serum (-1-PI concentration and age in the control group of males was significant (r=-0.83, P<0.01). The alpha-1-PI concentration was found significantly higher in coronary atherosclerosis patients compared with control (2.14+/-0.6 and 1.68+/-0.3 g/l respectively, P<0.05). The alpha-1-PI concentration was found to dependent on the apoB/apoA-1 ratio: it was higher in patients having apoB/apoA-1>1.0 than in patients with apoB/apoA-1<1.0 (2.4+/-0.6 and 2.04+/-0.5 g/l respectively, P<0.05). There was a significant correlation between alpha-1-PI concentration and apoB/apoA-1 ratio in blood serum of patients suffering from coronary atherosclerosis (r=0.25, P<0.05).


CONCLUSIONS
Derangements in the homeostasis of proteinase-antiproteinase system could be involved in destruction of the arterial wall connective tissue. The local as well as systemic inactivation of alpha-1-PI in atherosclerosis process could be related with hyperlipidemia. Investigation of long-survivors support the suggestion that they are important antiatherogenic control group for evaluating the role of genetic determinants in atherogenesis. Congenital (alpha-1-PI deficiency, hyperlipidemia) and acquired (related to smoking, aging) imbalance of proteinase-antiproteinase system is considered to one of the atherogenic factors. Authors discuss the possible mechanisms of atherogenesis related with imbalance of proteinase-antiproteinase system.
Stakisaitis
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Vilnius University Medical Faculty, Vilnius, Lithuania. donatasstakisaitis@vvkt.it
Basys
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Benetis
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003324:Coronary Artery Disease / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000515:alpha 1-Antitrypsin