Abstract 662: Maternal Soy Protein Diet Ameliorates Atherosclerotic Lesions in ApoE-Deficient Mice Offspring by Promoting Anti-inflammatory Responses Through Epigenetic Changes

Abstract

Maternal hypercholesterolemia has been implicated with an earlier onset of atherosclerotic lesions in neonatal offspring. In this study, we investigated whether gestational exposure to soy protein isolate (SPI) diet (maternal diet) primes the vessel wall to attenuate development of atherosclerosis in adult F1 offspring. Pregnant apolipoprotein E knockout (apoE-/-) female mice were fed SPI diet until postnatal day 21 (PND21) of the offspring (SPI-offspring). At PND21, SPI-offspring was switched to casein (CAS) diet until PND140. Mice fed CAS throughout the lifetime (gestation to adult) were used as control (CAS-offspring). Atherosclerotic lesions in aortic sinus were reduced in SPI-offspring compared with CAS-offspring. Total cholesterol levels in CAS- or SPI-offspring, and CAS- or SPI-fed dams were not different suggesting that alternative mechanism(s) contributes to the athero-protective effect of gestational SPI diet. Aortic VCAM-1, MCP-1 and TNF-α mRNA and protein expression were elevated in CAS offspring, while expression of these molecules were 50% reduced in SPI-offspring. Interestingly, compared to CAS-offspring IFN-γ expression (Th1) was reduced, while expression of IL-10 (Th2/Treg), and IL-13 (Th2) expression was increased in SPI-offspring, suggesting that Th2/Treg bias could have contributed to the athero-protective effect. DNA methylation analyses revealed gata3 and il13 promoter regions were hypomethylated in SPI-offspring. We conclude that in utero soy protein exposure inhibits susceptibility to atherosclerotic lesion formation by promoting anti-inflammatory responses through epigenetic regulation.