Abstract
The suppressive effect of porcine pancreatic elastase on experimental atherosclerosis was examined. Three groups of rabbits were studied for 53 weeks: one control group and two groups on a 1% cholesterol diet. Of the cholesterol-fed groups, one group received the 1% cholesterol diet alone, and the other group was administered intramuscularily with porcine pancreatic elastase (Eisai Co. Ltd., 10mg/rabbit/day).
The enzyme activity in sera of the three groups toward Suc-(Ala)3-pNA, a synthetic substrate of elastase, was significantly higher in elastase-treated rabbits for periods of 53 weeks. We estimated this activity as an elastase activity because elastatinal, a specific inhibitor of elastase, strongly inhibited the enzyme activity in sera of elastase-treated rabbits as well as the activity of porcine pancreatic elastase used for administration.
Treatment with elastase suppressed the elevations of serum cholesterol and triglyceride levels and calcium concentrations induced by the cholesterol diet. Rabbits given the cholesterol diet without elastase had a high content of cholesterol, triglyceride and calcium in aortic elastin as well as in aortic tissue. However, in rabbits treated with elastase, these components in both aortic tissue and elastin were reduced markedly, especially in elastin. A content of aortic elastin decreased in rabbits fed the cholesterol diet without elastase, but was restored in rabbits treated with elastase. Amino acid compositions of the isolated elastin preparations from aortas of untreated rabbits on the cholesterol diet showed a marked increase in polar amino acids and a significant decrease in cross-linking amino acids. However, treatment with elastase suppressed these changes in amino acids in elastin.
In microscopic studies on aortic media of the three groups, as compared to control rabbits, rabbits receiving the cholesterol diet without elastase showed not only severely deranged and fragmented elastic fibers but also heavy accumulations of calcium and lipids on the damaged elastic fibers. However, in rabbits treated with elastase, elastic fibers were almost normal and there was little accumulation of calcium and lipids on these elastic fibers except for a few deposits of calcium and lipids around the internal elastic lamina.
It was demonstrated from these biochemical and morphological studies that treatment with elastase resulted in a marked suppression of atherosclerosis. In particular, the prevention of alteration of elastin may play an important role in the antiatherogenic effect of elastase.
