Pitavastatin inhibits intimal hyperplasia in rabbit vein graft. 2008

Hiromine Fujita, and Hiroshi Banno, and Dai Yamanouchi, and Masayoshi Kobayashi, and Kiyohito Yamamoto, and Kimihiro Komori
Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

BACKGROUND The autologous saphenous vein graft is currently the most suitable conduit for arterial bypass of the lower limbs. Various approaches have been attempted to control vein graft intimal hyperplasia, and several recent reports have suggested that statin use may be linked to improved patency of vein grafts. In this study, the efficacy of pitavastatin was evaluated on intimal hyperplasia and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. METHODS Rabbits were fed regular rabbit chow, and in half of them, pitavastatin (1 mg/kg/d) was administered. A week after starting the treatment, jugular vein was implanted into the carotid artery. At 2 and 4 wk after the operation, vein grafts were harvested, and intimal hyperplasia of vein grafts were assessed. Cell proliferation in neointima was determined by proliferative cell nuclear antigen and Ki-67 stain 2 wk after implantation. In addition, the effect of pitavastatin on midkine, a heparin-binding growth factor, expressed in vein grafts was analyzed by Western blotting. RESULTS The intimal hyperplasia in the pitavastatin group was significantly suppressed compared with the control group. Both proliferative cell nuclear antigen and Ki-67 labeling index were significantly lower in the pitavastatin group, and pitavastatin significantly reduced midkine expression of vein graft. CONCLUSIONS These results demonstrate the efficacy of pitavastatin in reducing the degree of intimal hyperplasia of rabbit autologous vein grafts under normocholesterolemic condition. The mechanism of inhibition of intimal hyperplasia might be associated with midkine suppression.

UI MeSH Term Description Entries
D006965 Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells. Hyperplasias
D007601 Jugular Veins Veins in the neck which drain the brain, face, and neck into the brachiocephalic or subclavian veins. Jugular Vein,Vein, Jugular,Veins, Jugular
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008297 Male Males
D011804 Quinolines
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000078792 Midkine A developmentally regulated, HEPARIN-binding secreted growth factor homologous to pleiotrophin (PTN). It regulates cell proliferation through its interaction with ANAPLASTIC LYMPHOMA KINASE (ALK) and is involved in the formation of NEOINTIMA following arterial injury. Amphiregulin-Associated Protein,Cytokine MK,Amphiregulin Associated Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001026 Coronary Artery Bypass Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. Aortocoronary Bypass,Bypass, Coronary Artery,Bypass Surgery, Coronary Artery,Coronary Artery Bypass Grafting,Coronary Artery Bypass Surgery,Aortocoronary Bypasses,Artery Bypass, Coronary,Artery Bypasses, Coronary,Bypass, Aortocoronary,Bypasses, Aortocoronary,Bypasses, Coronary Artery,Coronary Artery Bypasses

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