Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

Toxicol Appl Pharmacol. 2011 Dec 15;257(3):405-11. doi: 10.1016/j.taap.2011.09.024. Epub 2011 Oct 6.

Abstract

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE(-/-)) mice treated or not with kaempferol (50 or 100mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE(-/-) mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE(-/-) mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Apolipoproteins E / genetics*
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Gene Expression Regulation / drug effects
  • Hyaluronan Receptors / drug effects*
  • Hyaluronan Receptors / metabolism
  • Kaempferols / administration & dosage
  • Kaempferols / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteopontin / blood
  • Osteopontin / drug effects*
  • Osteopontin / metabolism
  • Reactive Oxygen Species / metabolism
  • Vasodilation / drug effects

Substances

  • Apolipoproteins E
  • Hyaluronan Receptors
  • Kaempferols
  • Reactive Oxygen Species
  • Osteopontin
  • kaempferol