Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model

Recently it has been shown that protease therapy amelioratescertain immune-mediated diseases. Thus we studied the effectof administration of a protease mixture on aortic transplantarteriosclerosis in rats. Segments of abdominal aorta from SHRstrain were transplanted orthotopically into WKY recipients.Two groups of allografted rats were used. One group (n=8) wastreated with daily intraperitoneal injections of 12 mg of aprotease formulation containing trypsin, bromelain and rutosid,and another group (n=8) with placebo. Eight WKY rats were transplantedwith syngenic aortas and treated with placebo. After 8 weeks,structural changes of the grafted segment were evaluated bymorphometric analysis of formalin-fixed sections with specificstains. In untreated allografts there was a marked intimal thickening,medial necrosis with disruption of elastic fibres, and inflammatoryinfiltrates in the adventitia. Administration of proteases inhibitedformation of neointima by 59.0% when cross-sectional areas werecompared (80±11 versus 195±11 µm², P<0.01;protease-versus placebo-treated allograft recipients respectively)and decreased medial injury as estimated by the integrity ofelastic fibres and smooth-muscle cell density. Thus, in an experimentalmodel of rat aortic allograft, protease administration amelioratesrejection-induced arterial wall remodelling.