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.
Publication Date: 2004-12-07 PubMed ID: 15585561DOI: 10.1210/jc.2004-0939Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates the impact of soy isoflavones (IF) and conjugated equine estrogens (CEE) on inflammation markers in monkeys with atherosclerosis (a type of heart disease) who are also ovariectomized (have their ovaries surgically removed). Results showed that both substances reduced some inflammatory markers, implying a possible protective effect against atherosclerosis.
Study Design and Treatments
- The researchers used a three-year study on ovariectomized monkeys that consumed a diet moderately causing atherosclerosis. To assess the effects of dietary soy isoflavones and conjugated equine estrogens, they divided the monkeys into three treatment groups: a control group where monkeys received an alcohol-extracted soy-protein-based diet with low IF content, one group with CEE added to the control diet, and another group with IF consumed as part of unextracted soy protein isolate.
Results and Findings
- Both IF and CEE cut down serum soluble vascular cell adhesion molecule-1 (sVCAM-1), a protein that’s linked with inflammation.
- CEE reduced serum monocyte chemoattractant protein (MCP)-1, a substance that attracts white blood cells to the site of inflammation, but IF didn’t have the same effect.
- Neither IF nor CEE had noticeable effects on serum IL-6, soluble E-selectin, or C-reactive protein, three markers that are related to inflammation.
- They found significant correlations between serum MCP-1 and IL-6 and atherosclerosis in the iliac and carotid arteries. In addition, MCP-1 had a strong association with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling.
Conclusion
- From the results, the researchers concluded that, in their chosen nonhuman primate model of atherosclerosis, this dose of soy IF had an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE also extended to MCP1.
- They posited that the protective effects against atherosclerosis of IF and CEE might be mediated partially by their effects on VCAM-1. However, they noted that the places where IF inhibits sVCAM-1 production aren’t known yet, but it could be the liver and/or the cardiovascular system as likely places.
Cite This Article
APA
Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, Anthony MS, Blair RM, Wagner JD, Clarkson TB.
(2004).
Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys.
J Clin Endocrinol Metab, 90(3), 1734-1740.
https://doi.org/10.1210/jc.2004-0939 Publication
Researcher Affiliations
- Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, North Carolina 27157-1040, USA. register@wfubmc.edu
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
Citations
This article has been cited 24 times.- Song X, Wang X, Wang D, Zheng Z, Li J, Li Y. Natural drugs targeting inflammation pathways can be used to treat atherosclerosis. Front Pharmacol 2022;13:998944.
- Khodarahmi M, Foroumandi E, Asghari Jafarabadi M. Effects of soy intake on circulating levels of TNF-α and interleukin-6: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2021 Mar;60(2):581-601.
- Testerman TL, Semino-Mora C, Cann JA, Qiang B, Peña EA, Liu H, Olsen CH, Chen H, Appt SE, Kaplan JR, Register TC, Merrell DS, Dubois A. Both diet and Helicobacter pylori infection contribute to atherosclerosis in pre- and postmenopausal cynomolgus monkeys. PLoS One 2019;14(9):e0222001.
- Mahler SA, Register TC, Riley RF, D'Agostino RB Jr, Stopyra JP, Miller CD. Monocyte Chemoattractant Protein-1 as a Predictor of Coronary Atherosclerosis in Patients Receiving Coronary Angiography. Crit Pathw Cardiol 2018 Jun;17(2):105-110.
- DeBo RJ, Lees CJ, Dugan GO, Caudell DL, Michalson KT, Hanbury DB, Kavanagh K, Cline JM, Register TC. Late Effects of Total-Body Gamma Irradiation on Cardiac Structure and Function in Male Rhesus Macaques. Radiat Res 2016 Jul;186(1):55-64.
- Register TC, Appt SE, Clarkson TB. Atherosclerosis and Vascular Biologic Responses to Estrogens: Histologic, Immunohistochemical, Biochemical, and Molecular Methods. Methods Mol Biol 2016;1366:517-532.
- den Hartigh LJ, Wang S, Goodspeed L, Ding Y, Averill M, Subramanian S, Wietecha T, O'Brien KD, Chait A. Deletion of serum amyloid A3 improves high fat high sucrose diet-induced adipose tissue inflammation and hyperlipidemia in female mice. PLoS One 2014;9(9):e108564.
- Lee AR, Pechenino AS, Dong H, Hammock BD, Knowlton AA. Aging, estrogen loss and epoxyeicosatrienoic acids (EETs). PLoS One 2013;8(8):e70719.
- Jorgensen MJ, Aycock ST, Clarkson TB, Kaplan JR. Effects of a Western-type diet on plasma lipids and other cardiometabolic risk factors in African green monkeys (Chlorocebus aethiops sabaeus). J Am Assoc Lab Anim Sci 2013 Jul;52(4):448-53.
- Sophonsritsuk A, Appt SE, Clarkson TB, Shively CA, Espeland MA, Register TC. Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause. Menopause 2013 May;20(5):540-7.
- Murea M, Register TC, Divers J, Bowden DW, Carr JJ, Hightower CR, Xu J, Smith SC, Hruska KA, Langefeld CD, Freedman BI. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study. BMC Nephrol 2012 Nov 14;13:148.
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- Babu PV, Si H, Fu Z, Zhen W, Liu D. Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice. J Nutr 2012 Apr;142(4):724-30.
- Wood CE, Boue SM, Collins-Burow BM, Rhodes LV, Register TC, Cline JM, Dewi FN, Burow ME. Glyceollin-elicited soy protein consumption induces distinct transcriptional effects as compared to standard soy protein. J Agric Food Chem 2012 Jan 11;60(1):81-6.
- Appt SE, Chen H, Goode AK, Hoyer PB, Clarkson TB, Adams MR, Wilson ME, Franke AA, Kaplan JR. The effect of diet and cardiovascular risk on ovarian aging in cynomolgus monkeys (Macaca fascicularis). Menopause 2010 Jul;17(4):741-8.
- Appt SE, Ethun KF. Reproductive aging and risk for chronic disease: Insights from studies of nonhuman primates. Maturitas 2010 Sep;67(1):7-14.
- Register TC. Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis). Am J Primatol 2009 Sep;71(9):766-75.
- Maskarinec G, Steude JS, Franke AA, Cooney RV. Inflammatory markers in a 2-year soy intervention among premenopausal women. J Inflamm (Lond) 2009 Apr 7;6:9.
- Scott LM, Durant P, Leone-Kabler S, Wood CE, Register TC, Townsend A, Cline JM. Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes. J Steroid Biochem Mol Biol 2008 Dec;112(4-5):179-85.
- Scott LM, Xu X, Veenstra TD, Tooze JA, Wood CE, Register TC, Kock ND, Cline JM. Past oral contraceptive use and current dietary soy isoflavones influence estrogen metabolism in postmenopausal monkeys (Macaca fascicularis). Cancer Epidemiol Biomarkers Prev 2008 Oct;17(10):2594-602.
- Walker SE, Register TC, Appt SE, Adams MR, Clarkson TB, Chen H, Isom S, Franke AA, Kaplan JR. Plasma lipid-dependent and -independent effects of dietary soy protein and social status on atherogenesis in premenopausal monkeys: implications for postmenopausal atherosclerosis burden. Menopause 2008 Sep-Oct;15(5):950-7.
- Walker SE, Adams MR, Franke AA, Register TC. Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys. Atherosclerosis 2008 Jan;196(1):106-113.
- Adams MR, Anthony MS, Chen H, Clarkson TB. Replacement of dietary soy protein isolate with concentrates of soy 7S or 11S globulin has minimal or no effects on plasma lipoprotein profiles and biomarkers of coronary risk in monkeys. Atherosclerosis 2008 Jan;196(1):76-80.
- Gholami A, Amirkalali B, Hariri M. Can soy isoflavones in combination with soy protein change serum levels of C-reactive protein among patients with chronic inflammatory diseases? A systematic review and meta-analysis on randomized controlled trials. J Health Popul Nutr 2025 May 12;44(1):154.
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