Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression.
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.
Nagarajan
Shanmugam
S
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. nagarajanshanmugam@uams.edu
Burris
Ramona L
RL
Stewart
Bradford W
BW
Wilkerson
James E
JE
Badger
Thomas M
TM
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology* / Q000517:prevention & control*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D030262:Soybean Proteins / Q000494:pharmacology*
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004044:Dietary Proteins; D030262:Soybean Proteins