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Plasma lipid-dependent and -independent effects of dietary soy protein and social status on atherogenesis in premenopausal monkeys: implications for postmenopausal atherosclerosis burden

Walker, Sara E. MS1,2; Register, Thomas C. PhD1,2; Appt, Susan E. DVM1,2; Adams, Michael R. DVM1,2; Clarkson, Thomas B. DVM1,2; Chen, Haiying PhD2; Isom, Scott MS2; Franke, Adrian A. PhD3; Kaplan, Jay R. PhD1,2

doi: 10.1097/gme.0b013e3181612cef

Objective: Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. The objective of this study was to determine the effects of dietary soy protein isolate (SPI) and social status on atherogenesis and arterial gene expression in a premenopausal monkey model.

Design: Socially housed premenopausal cynomolgus macaques (n = 84) were fed an atherogenic diet deriving protein from casein/lactalbumin or SPI (containing 1.88 mg isoflavones/g). After 36 months of diet consumption, iliac artery biopsies were assessed for atherosclerosis and expression of mRNA transcripts related to inflammation, macrophage and T-cell content, and estrogen receptors (ERs).

Results: SPI reduced plaque size (P < 0.05), total plasma cholesterol, non-high-density lipoprotein cholesterol (HDLc), and the total plasma cholesterol/HDLc ratio (all P < 0.003), while increasing triglycerides (P < 0.006) and HDLc (P < 0.0001). Arterial mRNA for CD68 (P < 0.001), CD3 (P < 0.02), and CD4 (P < 0.001) and inflammatory markers monocyte chemotactic protein-1, intercellular adhesion molecule-1, and interleukin-6 (all P < 0.0001) were also lower in the group receiving SPI. For most outcomes, this effect remained even after adjustments for plaque size and plasma lipid concentrations. Arterial ER-α was inversely associated with atherosclerosis (P < 0.02) and increased with SPI (P < 0.001). Subordinate monkeys had lower ER-β (P < 0.02) and higher interleukin-6 (P < 0.05) transcripts but did not differ from dominant monkeys in extent of atherosclerosis (P > 0.9).

Conclusions: Premenopausal consumption of SPI had plasma lipid-independent beneficial effects on the pathobiological processes involved in atherosclerotic plaque development, thus potentially establishing the basis for reduced postmenopausal complications. Dominant social status provided similar, albeit less extensive, benefits in risk markers.

In a monkey model of atherosclerosis, premenopausal consumption of dietary soy protein produced plasma lipid-independent beneficial effects on the pathobiological processes involved in atherosclerotic plaque development, thus establishing the possibility of cardiovascular benefits of soy for postmenopausal women despite only minor effects on plasma lipid profiles.

From the 1Wake Forest University Primate Center and Section on Comparative Medicine and 2Wake Forest University School of Medicine, Winston-Salem, NC; and 3The Cancer Research Center of Hawaii, Honolulu, HI.

Received August 26, 2007; revised and accepted November 5, 2007.

Funding/support: This project was supported in part by National Institutes of Health Grants HL45666 and HL 79421 (J.R.K.), RR020890 (A.A.F.), AG18170 (T.C.R.), and AG28641 (T.C.R.).

Financial disclosure: None reported.

Address correspondence to: Thomas C. Register, PhD, Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1040. E-mail:

©2008The North American Menopause Society