MISC

2007年1月

Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes

CIRCULATION JOURNAL
  • Yan Chen
  • ,
  • Koji Ohmori
  • ,
  • Mizuki Mizukawa
  • ,
  • Junji Yoshida
  • ,
  • Yu Zeng
  • ,
  • Ling Zhang
  • ,
  • Kaori Shinomiya
  • ,
  • Hiroaki Kosaka
  • ,
  • Masakazu Kohno

71
1
開始ページ
144
終了ページ
152
記述言語
英語
掲載種別
DOI
10.1253/circj.71.144
出版者・発行元
JAPANESE CIRCULATION SOCIETY

Background Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS).
Methods and Results The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-a, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta 1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography.
Conclusions The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.

Web of Science ® 被引用回数 : 38

リンク情報
DOI
https://doi.org/10.1253/circj.71.144
CiNii Articles
http://ci.nii.ac.jp/naid/110006151879
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000243166900024&DestApp=WOS_CPL