Dietary Soy Protein Isolate Ameliorates Atherosclerotic Lesions in Apolipoprotein E-Deficient Mice Potentially by Inhibiting Monocyte Chemoattractant Protein-1 Expression1, ,3

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.

Antiatherogenic Effect of Antioxidant Polyphenols from <i>Phellinus baumii </i> in Apolipoprotein E-Deficient Mice

“…MCP-1, a member of the CC chemokines, is involved in both recruitment of monocytes and lipid deposition into arterial walls, thereby enhancing the progression of atherosclerosis [19]. Previous studies have reported that both absence of MCP-1 and inhibition of adhesion molecule expression ameliorate atherosclerosis in various atherosclerotic models including low-density lipoprotein receptor-deficient mice [18], apoE–/– [20] mice, and high-cholesterol-fed rabbits [21,22]. Therefore, downregulation of proatherogenic genes may have ameliorated the development of atherosclerotic lesions in this study.…”

Polyamines - The Principal Candidate Substance of Soybean-Induced Health

“…However, studies have shown that atherosclerotic lesions are reduced in atherosclerosis-susceptible apolipoprotein E knockout (apoE-/-) mice fed a soy-containing diet despite unchanged serum lipid levels (Adams et al, 2002;Nagarajan et al, 2008). Moreover, intervention studies in humans have shown that the favorable effects of soy protein on vascular function are independent of lipid and antioxidant effects (Steinberg et al, 2003).…”

“…Moreover, intervention studies in humans have shown that the favorable effects of soy protein on vascular function are independent of lipid and antioxidant effects (Steinberg et al, 2003). Soy protein has anti-inflammatory properties, and the mechanisms of soymediated inhibition of atherosclerosis are considered to be anti-inflammatory (Nagarajan et al, 2008). The importance of isoflavones has been disputed because the favorable effects of soy can be elicited by soy protein devoid of isoflavones (Balmir et al, 1996;Nagarajan et al, 2008;Song et al, 2003).…”

“…Soy protein has anti-inflammatory properties, and the mechanisms of soymediated inhibition of atherosclerosis are considered to be anti-inflammatory (Nagarajan et al, 2008). The importance of isoflavones has been disputed because the favorable effects of soy can be elicited by soy protein devoid of isoflavones (Balmir et al, 1996;Nagarajan et al, 2008;Song et al, 2003). The effects of various fatty acids on inflammation are well established.…”

Biochemical Evidence of Atherosclerosis Progression Mediated by Increased Oxidative Stress in Apolipoprotein E–Deficient Spontaneously Hyperlipidemic Mice Exposed to Chronic Cigarette Smoke

“…Apolipoprotein E (ApoE)-deficient mice develop severe hypercholesterolemia and atherosclerotic lesions in a manner similar to humans (23,24), and they are used extensively as a model for atherosclerosis research (25). In these mice, cigarette smoking has been reported to accelerate atherogenesis (26,27).…”