Ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with inhibition of cholesterol absorption in humans

Kotaro Nochioka, Shin ichi Tanaka, Masanobu Miura, Do e. Zhulanqiqige, Yoshihiro Fukumoto, Nobuyuki Shiba, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Background: Ezetimibe is an inhibitor of cholesterol absorption in the intestine. We examined whether ezetimibe improves endothelial function, and if so, what mechanisms are involved. Methods and Results: Nineteen healthy subjects (male/female 14/5; mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10 mg/day) or pravastatin (10 mg/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). Conclusions: 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.

Original languageEnglish
Pages (from-to)2023-2030
Number of pages8
JournalCirculation Journal
Volume76
Issue number8
DOIs
Publication statusPublished - 2012

Keywords

  • Ezetimibe
  • Flow-mediated dilatation
  • LDL cholesterol
  • Rho-kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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