Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-κB activation and peroxisome proliferator-activated receptor-gamma upregulation

J Immunol. 2010 Sep 15;185(6):3718-27. doi: 10.4049/jimmunol.1001043. Epub 2010 Aug 13.


Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II-induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1alpha. In an in vitro flow chamber system, t-RESV (1-10 microM) undermined the adhesion of human leukocytes under physiological flow to Ang-II-activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-kappaB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-gamma in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-gamma also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / physiology
  • Animals
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cell Communication / drug effects
  • Cell Communication / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Inflammation Mediators / administration & dosage
  • Inflammation Mediators / chemistry
  • Inflammation Mediators / pharmacology*
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Ovariectomy
  • PPAR gamma / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stereoisomerism
  • Stilbenes / administration & dosage
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology*


  • Angiogenesis Inhibitors
  • Inflammation Mediators
  • NF-kappa B
  • PPAR gamma
  • Stilbenes
  • Angiotensin II
  • Resveratrol