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Nutritional Immunology

Dietary Soy Protein Isolate Ameliorates Atherosclerotic Lesions in Apolipoprotein E-Deficient Mice Potentially by Inhibiting Monocyte Chemoattractant Protein-1 Expression^1–3,

⁴ Arkansas Children's Nutrition Center, ⁵ Department of Microbiology and Immunology, and ⁶ Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205

^* To whom correspondence should be addressed. E-mail: nagarajanshanmugam{at}uams.edu.

Soy-based diets reportedly protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of a soy-based diet was addressed using the apolipoprotein E knockout (apoE–/–) mice fed soy protein isolate (SPI) associated with or without phytochemicals (SPI⁺ and SPI^–, respectively) or casein (CAS). Reduced atherosclerotic lesions were observed in aortic sinus and enface analyses of the descending aorta in SPI⁺- or SPI^–-fed apoE–/– mice compared with CAS-fed mice. SPI⁺-fed mice showed 20% fewer lesions compared with SPI^–-fed mice. Plasma lipid profiles did not differ among the 3 groups, suggesting alternative mechanism(s) could have contributed to the atheroprotective effect of soy-based diets. Real-time quantitative PCR analyses of proximal aorta showed reduced expression of monocyte chemoattractant protein-1 (MCP-1), a monocyte chemokine, in mice fed both soy-based diets compared with the CAS-fed mice. These findings paralleled the reduced number of macrophages observed in the lesion site in the aorta of SPI⁺- or SPI^–-fed mice compared with CAS-fed mice. In an in vitro LPS-induced inflammation model, soy isoflavones (genistein, daidzein, and equol alone or in combination) dose dependently inhibited LPS-induced MCP-1 secretion by macrophages, suggesting a role for soy isoflavones for the protective in vivo effects. Collectively, these findings suggest that the reduction in atherosclerotic lesions observed in mice fed the soy-based diet is mediated in part by inhibition of MCP-1 that could result in reduced monocyte migration, an early event during atherogenesis.