Plaque-Stabilizing Effect of Pitavastatin in Watanabe Heritable Hyperlipidemic(WHHL) Rabbits.

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  • Suzuki Hideo
    Tokyo New Drug Research Laboratories I, Pharmaceutical Division, Kowa Co, Ltd
  • Kobayashi Hideyuki
    Tokyo New Drug Research Laboratories I, Pharmaceutical Division, Kowa Co, Ltd
  • Sato Fumiyasu
    Tokyo New Drug Research Laboratories I, Pharmaceutical Division, Kowa Co, Ltd
  • Yonemitsu Yoshikazu
    Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University
  • Nakashima Yutaka
    Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University
  • Sueishi Katsuo
    Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University

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Abstract

This study investigated the effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor with strong cholesterol-lowering activity, on the composition of atherosclerotic plaque. Pitavastatin ( 0.5mg/kg ) was administered to Watanabe heritable hyperlipidemic ( WHHL ) rabbits for 16 weeks, with the result that plasma total cholesterol ( TC ), very low density lipoprotein ( VLDL )-C, intermediate density lipoprotein ( IDL )-C and low density lipoprotein ( LDL )-C decreased by 28.6, 60.0, 42.3 and 21.7%, respectively. In the aorta, pitavastatin reduced the area of the lesion by 38.6%. In the pitavastatin group, the macrophage-positive area in the aortic plaque was reduced by 39.4%, and the areas occupied by collagen and a-smooth muscle actin ( α -SMA )-positive area increased by 66.4 and 91.7%, respectively. In the aortic arch, pitavastatin increased the average thickness of α-SMA in the plaque by 96.7% and reduced the vulnerability index by 76.0%. Furthermore, pitavastatin reduced the positive areas of monocyte chemoattractant protein ( MCP )-1, matrix metalloproteinase ( MMP )-3 and MMP-9 by 39.1, 40.6 and 52.3%, respectively. These results indicated that pitavastatin had an excellent lipid-lowering effect in WHHL rabbits, suppressing the progression of atherosclerosis and stabilizing atherosclerotic plaque.

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