Chymase activity is closely related with plaque vulnerability in a hamster model of atherosclerosis

Objective: To test the hypothesis that stimulation of chymase secretion may contribute to plaque vulnerability and inhibition of chymase activity may enhance plaque stability. Methods and results: Sixty eight-week-old male Syrian golden hamsters were randomly divided into normal control group, high-cholesterol (HC) treated group, HC+ovalbumin treated group and HC+tranilast treated group. The normal control group received a normal diet while the other three intervention groups received a high-cholesterol diet for 15 weeks. Hamsters in the HC+ovalbumin treated group underwent transcatheter pharmacological triggering at the end of week 15 after antigen sensitization and those in the HC+tranilast treated group were given tranilast intragastrically for 3 weeks before euthanasia. Serological, ultrasonographic, pathologic, immunohistochemical, and gene expression studies were performed in all animals. The total number of mast cells, proportion of degranulated mast cells and the number of extracellular granules in plaques, the apoptosis rate of vascular smooth cells, the local activities of chymase, the concentration of Ang II and the expression levels of inflammatory markers as well as plaque vulnerability index all increased significantly in HC+ovalbumin treated group, but remarkably decreased in HC+tranilast treated group, in comparison with the HC treated group. These results suggest that stimulation of chymase secretion contributes to plaque vulnerability while inhibition of chymase activity enhances plaque stability. We conclude that chymase activity provides a promising therapeutic target in the stabilization of atherosclerotic plaques. (C) 2009 Elsevier Ireland Ltd. All rights reserved.