Ezetimibe Improves Endothelial Function and Inhibits Rho-Kinase Activity Associated With Inhibition of Cholesterol Absorption in Humans

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Author(s)

    • NOCHIOKA Kotaro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • TANAKA Shin-ichi
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • MIURA Masanobu
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • ZHULANQIQIGE Do. e
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • FUKUMOTO Yoshihiro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • SHIBA Nobuyuki
    • Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • SHIMOKAWA Hiroaki
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

Abstract

<b><i>Background:</i></b> Ezetimibe is an inhibitor of cholesterol absorption in the intestine. We examined whether ezetimibe improves endothelial function, and if so, what mechanisms are involved. <b><i>Methods and Results:</i></b> Nineteen healthy subjects (male/female 14/5; mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner with a 4-week washout interval. Lipid profiles, flow-mediated dilatation (FMD) and Rho-kinase activity of circulating leukocytes (the extent of phosphorylation of myosin binding subunit, a Rho-kinase substrate) were examined. We also evaluated remnant-like particle cholesterol (RLP-C) known as an up-regulator of Rho-kinase and cholesterol absorption status by measuring cholestanol and campesterol/lathosterol ratio (CLR) (both absorption markers). Although ezetimibe and pravastatin equally reduced low-density lipoprotein cholesterol (E: -25% vs. P: -21%), the CLR was reduced by ezetimibe but was rather increased by pravastatin (E: -41% vs. P: +37%; P<0.01). Reduction in RLP-C by ezetimibe was greater compared with pravastatin (E: -33% vs. P: -14%; P<0.05). Importantly, ezetimibe significantly improved FMD (26%, P<0.05) and reduced Rho-kinase activity (-21%, P<0.05), whereas pravastatin had no such effects. A significant correlation was noted between the reduction in cholestanol and the improvement in FMD (P<0.05). <b><i>Conclusions:</i></b> These results indicate that ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with the inhibition of cholesterol absorption, suggesting novel anti-atherogenic effects of the agent in humans.  (<i>Circ J</i> 2012; <b>76:</b> 2023–2030)<br>

Journal

  • Circulation Journal

    Circulation Journal 76(8), 2023-2030, 2012-07-25

    The Japanese Circulation Society

References:  31

Cited by:  1

Codes

  • NII Article ID (NAID)
    10030505144
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  J-STAGE 
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