PMID- 18203900 OWN - NLM STAT- MEDLINE DCOM- 20080214 LR - 20230216 IS - 1541-6100 (Electronic) IS - 0022-3166 (Linking) VI - 138 IP - 2 DP - 2008 Feb TI - Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression. PG - 332-7 AB - 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. FAU - Nagarajan, Shanmugam AU - Nagarajan S AD - Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. nagarajanshanmugam@uams.edu FAU - Burris, Ramona L AU - Burris RL FAU - Stewart, Bradford W AU - Stewart BW FAU - Wilkerson, James E AU - Wilkerson JE FAU - Badger, Thomas M AU - Badger TM LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Apolipoproteins E) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Dietary Proteins) RN - 0 (Soybean Proteins) SB - IM MH - Animals MH - Aorta/pathology MH - Apolipoproteins E/*deficiency/genetics MH - Atherosclerosis/*pathology/*prevention & control MH - Cell Line MH - Chemokine CCL2/genetics/*metabolism MH - Diet MH - Dietary Proteins/*pharmacology MH - Down-Regulation/*drug effects MH - Female MH - Humans MH - Macrophages/drug effects MH - Mice MH - Mice, Knockout MH - Soybean Proteins/*pharmacology EDAT- 2008/01/22 09:00 MHDA- 2008/02/15 09:00 CRDT- 2008/01/22 09:00 PHST- 2008/01/22 09:00 [pubmed] PHST- 2008/02/15 09:00 [medline] PHST- 2008/01/22 09:00 [entrez] AID - S0022-3166(22)09547-5 [pii] AID - 10.1093/jn/138.2.332 [doi] PST - ppublish SO - J Nutr. 2008 Feb;138(2):332-7. doi: 10.1093/jn/138.2.332.