Anti-inflammatory effects of isoflavones are dependent on flow and human endothelial cell PPAR gamma

Balu K. Chacko, Robert T. Chandler, Tracy L. D'Alessandro, Ameya Mundhekar, Nicholas K. H. Khoo, Nigel Botting, Stephen Barnes, Rakesh P. Patel

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

The mechanisms by which isoflavones protect against inflammatory vascular disease remain unclear. Our previous observations suggest that one mechanism involves inhibition of monocyte-endothelial cell interactions in a process that is absolutely dependent on flow. The molecular mechanisms involved and the effects of structurally distinct isoflavones on this process are not known and are investigated herein. Using static and flow-dependent monocyte adhesion assays, our data show that exposure of endothelial cells to biologically relevant concentrations of isoflavones inhibits subsequent TNF-alpha induced monocyte adhesion only during flow. This inhibition involved activating endothelial PPAR gamma by stimulating promoter sequences containing the PPAR gamma response element by isoflavones and attenuating antiadhesive effects by siRNA targeting of PPAR gamma. A comparison of structurally distinct isoflavones suggested a critical role for the A-ring. Using chlorinated derivatives of daidzein, a key structural requirement for PPAR gamma agonist activity appears to be the presence of the 7-OH group and the lack of chlorine at the 6- or 8-positions in the A-ring. Collectively, these data support 1) a novel flow-dependent anti-inflammatory mechanism for PPAR gamma ligands in vascular endothelial cells and 2) exemplify the current concepts of nutrients modulating disease via regulating specific cell signaling pathways.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
JournalJournal of Nutrition
Volume137
Publication statusPublished - Feb 2007

Keywords

  • ACTIVATED RECEPTOR-GAMMA
  • LOW-DENSITY-LIPOPROTEIN
  • SOY ISOFLAVONES
  • PHYTOESTROGEN GENISTEIN
  • POSTMENOPAUSAL WOMEN
  • NITRIC-OXIDE
  • CARDIOVASCULAR HEALTH
  • MECHANISMS
  • OXIDATION
  • PROTEIN

Fingerprint

Dive into the research topics of 'Anti-inflammatory effects of isoflavones are dependent on flow and human endothelial cell PPAR gamma'. Together they form a unique fingerprint.

Cite this