The systemic enzyme therapy in experimental atherosclerosis
Dosenko
V.E., Zakharova V.P., Byc Y.V. The systemic enzyme therapy in
experimental atherosclerosis. Experimental cardiology 2000, No. 5-6,
pp. 87-94.
The etiology and
pathogenesis of atherosclerosis (AS), which is undoubtedly
influenced by modified lipoproteins and damaged arterial wall with
altered properties of blood vessel connective tissue is discussed.
The goal of this study was to estimate the effect of proteolytic
enzymes in the treatment and prophylaxis of AS. The elastolytic
system of serum and tissues was studied.22 adult chinchila rabbits
were included into the study. AS was simulated by means of feeding
0.75% cholesterol diet for 30 days. The animals were divided into
three groups: I – controls fed by a standard diet, II – received
only cholesterol diet, III – received cholesterol diet and
Phlogenzym at doses corresponding to the mean therapeutic dose for
men. After 30 days, the animals were sacrificed. Aortas were
homogenized and exploited for biochemical analysis. Blood was
sampled and serum was prepared. The activity of elastase was
determined using a specific chromogenic substrate. The amount of
total cholesterol was assayed. The stripes of aortas were fixed in
HCHO and prepared for histological examination. All data were
statistically evaluated by Student`s t-test.
In the course of AS modeling, a fundamental impairment of the system
elastase-inhibitors was discovered. The activity of elastase (mM/g
of protein or per 1 l of serum resp.), the content of a2
macroglobulin (a2 M) (mg/g of protein or g/l of serum resp.), and a1
proteinase inhibitor (mg / g of protein or g/l of serum resp.) were
measured. Changes of the coefficient inhibitors/elastase, which is a
real indicator of elastolytic system, were studied.
The comparison of elastase activity in aorta homogenates revealed,
however, an opposite trend: there was no difference in elastase
activity between groups I and II (2.52 ± 0.19 vs. 1.86 ± 0.44),
while there was a statistically significant increase (5.44 ± 1.15)
in the group III (Phlogenzym). The level of a2 M was statistically
significantly lower in the groups II and III (5.07 ± 1.89; 5.74 ±
1.62) in comparison to the control group (9.72 ± 0.74). The
coefficient of inhibitors/elastase was thus lowered in the
Phlogenzym group III (1.14) as compared to the groups I and II
(4.20; 3.30). In other words again, an increase of elastolytic
activity was found in the aorta tissue of Phlogenzym-treated
animals.
Histopathological examination revealed morfological changes of
fibrous structures of aorta, lysis of segments and loosened fibers
of elastic membranes in the group II (cholesterol fed animals).
Degeneration of collagen fibers was also observed. The
administration of Phlogenzym had a significant effect on the
elastolytic system of rabbits. The findings in animals treated by
Phlogenzym were less pronounced, collagen and elastic fibers
maintained its structure. The addition of proteolytic enzyme mixture
palliated pathological changes in the course of experimental
atherosclerosis.
Elastase is generally considered to cause a degradation of
intercellular proteins only. However, it may have a protective and
prophylactic effect against development of AS.
Elastase operates against
decrease of acetylcholin-induced relaxation and noradrenalin-induced
constriction and it has the ability to lower total cholesterol.
Purified pancreatic elastase (Elaszym) is authorized in Japan and it
is used for prophylaxis and treatment of AS. It contributes to the
decrease of arterial pressure and inhibits aging of arterial blood
vessel tissues. The authors suppose that the strong effect of
elastase against AS is not specific, and the same effect can be
achieved by other proteolytic enzymes administered orally because
they activate the same cell receptors.
Treating AS by a combination polyenzyme preparation is more advantageous
than just elastase monotherapy.