Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2008
Publication Date: 2/8/2008
Citation: Nagarajan, S., Burris, R.L., Stewart, B.W., Wilkerson, J.E., Badger, T.M. 2008. Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression. Journal of Nutrition. 138(2):332-337.
Interpretive Summary: Heart attack is caused by reduced blood flow to the heart. This is due to the thickening of blood vessels, also known as atherosclerosis. Asian populations consume diets high in soy. Studies have suggested that the decreased rate of heart disease may be due to their dietary consumption of soy. In the United States, more than 1 million infants a year are fed soy-based formula. Furthermore, the incidence of cardiovascular diseases is rising in obese children. Hence, we are interested in determining if soy can reduce the incidence of heart disease. In this study we examined the effect of eating soy on reducing atherosclerosis. We found that mice bred to develop atherosclerosis had fewer lesions in the aorta than mice fed the control diets made with casein. This study also demonstrated that the protective effects were due to the soy protein itself with minimal contribution from soy phytochemicals. Future research will determine any additional mechanisms contributing to the protective effect of soy.
Technical Abstract: 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.