Burris Ramona L, Vick Sarah C, Popovic Branimir, Fraungruber Pamelia E, Nagarajan Shanmugam
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Atherosclerosis. 2020 Nov;313:26-34. doi: 10.1016/j.atherosclerosis.2020.09.018. Epub 2020 Sep 22.
Maternal hypercholesterolemia has been implicated in earlier onset of atherosclerotic lesions in neonatal offspring. In this study, we investigated whether maternal exposure to soy protein isolate (SPI) diet attenuated the progression of atherosclerosis in F1 offspring.
Pregnant apolipoprotein E knockout (Apoe) female mice were fed SPI diet until postnatal day 21 (PND21) of the offspring (SPI-offspring). SPI-offspring were switched at PND21 to casein (CAS) diet until PND140. Mice fed CAS throughout their lifetime (gestation to adulthood) were used as controls (CAS-offspring).
Atherosclerotic lesions in the aortic sinuses were reduced in SPI-offspring compared with CAS-offspring. Total serum cholesterol levels in CAS-offspring or dams were comparable to levels in their SPI-counterparts, suggesting that alternative mechanisms contributed to the athero-protective effect of maternal SPI diet. Aortic VCAM-1, MCP-1, and TNF-α mRNA and protein expression, and expression of macrophage pro-inflammatory cytokines was reduced in SPI-offspring. Interestingly, CD4 T cells from SPI-offspring showed reduced IFN-γ expression (Th1), while the expression of IL-10 (Th2/Treg), and IL-13 (Th2) was increased. DNA methylation analyses revealed that anti-inflammatory T cell-associated Gata3 and Il13 promoter regions were hypomethylated in SPI-offspring. These findings suggest that anti-inflammatory macrophage and T cell response may have contributed to the athero-protective effect in SPI-offspring.
Our findings demonstrate that gestational and lactational soy diet exposure inhibits susceptibility to atherosclerotic lesion formation by promoting anti-inflammatory responses by macrophages and T cells.
母体高胆固醇血症与新生后代动脉粥样硬化病变的早期发生有关。在本研究中，我们调查了母体摄入大豆分离蛋白（SPI）饮食是否能减轻F1代后代动脉粥样硬化的进展。
给怀孕的载脂蛋白E基因敲除（Apoe）雌性小鼠喂食SPI饮食，直至后代出生后第21天（PND21）（SPI后代）。SPI后代在PND21时换为酪蛋白（CAS）饮食，直至PND140。终生喂食CAS的小鼠（从妊娠到成年）用作对照（CAS后代）。
与CAS后代相比，SPI后代主动脉窦中的动脉粥样硬化病变减少。CAS后代或母鼠的总血清胆固醇水平与其SPI对应物的水平相当，这表明其他机制促成了母体SPI饮食的抗动脉粥样硬化作用。SPI后代中主动脉VCAM-1、MCP-1和TNF-α的mRNA和蛋白表达以及巨噬细胞促炎细胞因子的表达均降低。有趣的是，SPI后代的CD4 T细胞显示IFN-γ表达（Th1）降低，而IL-10（Th2/Treg）和IL-13（Th2）的表达增加。DNA甲基化分析显示，抗炎性T细胞相关的Gata3和Il13启动子区域在SPI后代中低甲基化。这些发现表明，抗炎性巨噬细胞和T细胞反应可能促成了SPI后代的抗动脉粥样硬化作用。
我们的研究结果表明，孕期和哺乳期暴露于大豆饮食可通过促进巨噬细胞和T细胞的抗炎反应来抑制动脉粥样硬化病变形成的易感性。
