Plaque-stabilizing effect of pitavastatin in Watanabe heritable hyperlipidemic (WHHL) rabbits.

Hideo Suzuki, Hideyuki Kobayashi, Fumiyasu Sato, Yoshikazu Yonemitsu, Yutaka Nakashima, Katsuo Sueishi

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 ( alpha-SMA )-positive area increased by 66.4 and 91.7%, respectively. In the aortic arch, pitavastatin increased the average thickness of alpha-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.

Original languageEnglish
Pages (from-to)109-116
Number of pages8
JournalJournal of atherosclerosis and thrombosis
Volume10
Issue number2
DOIs
Publication statusPublished - 2003
Externally publishedYes

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Rabbits
Atherosclerotic Plaques
IDL Lipoproteins
VLDL Cholesterol
Matrix Metalloproteinase 3
Chemokine CCL2
Macrophages
Matrix Metalloproteinase 9
Arches
pitavastatin
Thoracic Aorta
LDL Lipoproteins
Smooth Muscle
Muscle
Aorta
Actins
Atherosclerosis
Oxidoreductases
Collagen
Cholesterol

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

Cite this

Plaque-stabilizing effect of pitavastatin in Watanabe heritable hyperlipidemic (WHHL) rabbits. / Suzuki, Hideo; Kobayashi, Hideyuki; Sato, Fumiyasu; Yonemitsu, Yoshikazu; Nakashima, Yutaka; Sueishi, Katsuo.

In: Journal of atherosclerosis and thrombosis, Vol. 10, No. 2, 2003, p. 109-116.

Research output: Contribution to journalArticle

Suzuki, Hideo ; Kobayashi, Hideyuki ; Sato, Fumiyasu ; Yonemitsu, Yoshikazu ; Nakashima, Yutaka ; Sueishi, Katsuo. / Plaque-stabilizing effect of pitavastatin in Watanabe heritable hyperlipidemic (WHHL) rabbits. In: Journal of atherosclerosis and thrombosis. 2003 ; Vol. 10, No. 2. pp. 109-116.
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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 ( alpha-SMA )-positive area increased by 66.4 and 91.7{\%}, respectively. In the aortic arch, pitavastatin increased the average thickness of alpha-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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