Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys

J Clin Endocrinol Metab. 2005 Mar;90(3):1734-40. doi: 10.1210/jc.2004-0939. Epub 2004 Dec 7.


The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to approximately 5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P = 1.00). Treatments did not affect serum IL-6 (P = 0.40), soluble E-selectin (P = 0.17), or C-reactive protein (P = 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01). We conclude that, in this well-established nonhuman primate model of atherosclerosis, this dose of soy IF provided an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE extended to both sVCAM-1 and MCP1. It is possible that the atheroprotective effects of IF and CEE are mediated, at least in part, by effects on VCAM-1. The sites of IF inhibitory effects on sVCAM-1 production are not known, but likely candidates include the liver and/or the cardiovascular system.

MeSH terms

  • Animals
  • Arteriosclerosis / drug therapy*
  • Arteriosclerosis / immunology*
  • Arteriosclerosis / pathology
  • Biomarkers / blood
  • Chemokine CCL2 / blood
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Isoflavones / pharmacology*
  • Macaca fascicularis
  • Matrix Metalloproteinase 9 / metabolism
  • Ovariectomy
  • Soybean Proteins / pharmacology*


  • Biomarkers
  • Chemokine CCL2
  • Estrogens, Conjugated (USP)
  • Isoflavones
  • Soybean Proteins
  • Matrix Metalloproteinase 9