Variation of elastase-type protease activity and elastin biosynthesis in rabbit aorta induced by cholesterol diet and immunization with elastin peptides.

Elastase-type proteases were shown to be produced by arterial smooth muscle cells and fibroblasts in culture and are probably involved in the development of the arterio-atherosclerotic process (1-4). The present investigation was aimed at the quantitative determination of the elastase-type enzyme activity in the aortas of rabbits submitted to two different athero-arteriosclerosis inducing treatments: high cholesterol diet and immunization with kappa-elastin peptides. Simultaneously we determined the incorporation of 14C-lysine in cross-linked elastin peptides by the surviving aorta extracts, determined with a synthetic substrate (Suc-(Ala)3-pNA) increased two fold after 1.5 month cholesterol diet, and three fold after 8 weeks of immunization with kappa-elastin in complete Freund's adjuvant. The incorporation of 14C-lysine in cross-linked elastin slightly increased (+20%) in cholesterol-fed aorta-explants and strongly decreased (-65%) in the immunized aorta-explants, on a DNA basis. These results confirm our contention that atherogenic stimuli produce an increase of elastase-type enzyme activity in the arterial wall. This increase appears to be correlated with elastic fibers degradation. It may also be accompanied by a decrease of elastin biosynthesis as in the kappa-elastin induced immuno-arteriosclerosis model.