title: Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys.
abstract: 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.
authors.affiliation: Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, North Carolina 27157-1040, USA. register@wfubmc.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cann
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kaplan
authors.forename: J Koudy
authors.initials: JK
authors.lastname: Williams
authors.forename: Michael R
authors.initials: MR
authors.lastname: Adams
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Mary S
authors.initials: MS
authors.lastname: Anthony
authors.forename: Robert M
authors.initials: RM
authors.lastname: Blair
authors.forename: Janice D
authors.initials: JD
authors.lastname: Wagner
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Clarkson
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D007529:Isoflavones / Q000494:pharmacology*; D008252:Macaca fascicularis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010052:Ovariectomy; D030262:Soybean Proteins / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D004966:Estrogens, Conjugated (USP); D007529:Isoflavones; D030262:Soybean Proteins; D020780:Matrix Metalloproteinase 9