title: Effects of oral administration of tripeptides derived from type I collagen (collagen tripeptide) on atherosclerosis development in hypercholesterolemic rabbits.
abstract: Digestion of type I collagen with a collagenase-type protease yields a collagen tripeptide (Ctp) fraction comprising Gly-X-Y sequences that exhibit diverse biological activities. We previously demonstrated that Ctp inhibits the proliferation and migration of cultured aortic smooth muscle cells (SMCs) in vitro. These cells contribute to the pathogenesis of atherosclerosis and other cardiovascular diseases. In order to evaluate the effects of Ctp on atherosclerosis development in vivo, here we used the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit model of familial hypercholesterolemia to determine the effects of oral administration of Ctp for three months. Ctp induced a significant decrease in the area occupied by atherosclerotic plaques in the aorta and in the level of total serum cholesterol. The components of atherosclerotic plaques underwent distinct changes, including reduction in the populations of macrophages and SMCs and a significant decrease in the proportion of macrophages to SMCs. Ctp administration decreased the number of cells in plaques that expressed proliferating cell nuclear antigen and the number of cells with oxidative damage to DNA as indicated by 8-hydroxy-2'-deoxyguanine detection. These findings are the first to define the mechanism underlying the inhibitory effects of Ctp on atherosclerosis development in hypercholesterolemic rabbits, and suggest that Ctp provides an effective therapy for treating atherosclerosis.
authors.affiliation: Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Lihua
authors.initials: L
authors.lastname: Tang
authors.affiliation: Central Research Institute, Jellice Co., Ltd., 4-4-1 Sakae, Tagajo-shi, Miyagi 985-0833, Japan. Electronic address: sakai@jellice.com.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Katsuda
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D024042:Collagen Type I / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits
chemical_list: D024042:Collagen Type I; D018809:Proliferating Cell Nuclear Antigen; C526216:collagen tripeptide Ctp, human; D002784:Cholesterol
keywords: Atherosclerosis; Collagen tripeptide; Kurosawa and Kusanagi-hypercholesterolemic rabbit; Plaque; Smooth muscle cells; Total cholesterol