Maternal exposure to soy diet reduces atheroma in hyperlipidemic F1 offspring mice by promoting macrophage and T cell anti-inflammatory responses.
Maternal exposure to soy diet reduces atheroma in hyperlipidemic F1 offspring mice by promoting macrophage and T cell anti-inflammatory responses.
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孕产妇暴露于大豆饮食可通过促进巨噬细胞和T细胞抗炎反应来减少高脂血脂F1后代小鼠的动脉瘤。
DOI：
10.1016/j.atherosclerosis.2020.09.018
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发表时间：
2020-11
期刊：
影响因子：
5.3
通讯作者：
Nagarajan S
中科院分区：
文献类型：
--
作者：
Burris RL;Vick SC;Popovic B;Fraungruber PE;Nagarajan S
母亲高胆固醇血症与新生儿后代动脉粥样硬化病变的早期发生有关。在这项研究中，我们调查了母亲摄入大豆分离蛋白 (SPI) 饮食是否会减轻 F1 后代动脉粥样硬化的进展。怀孕的载脂蛋白 E 敲除 (Apoe−/−) 雌性小鼠被喂食 SPI 饮食，直至其后代 (SPI-后代) 出生后第 21 天 (PND21)。 SPI 后代在 PND21 时改为酪蛋白 (CAS) 饮食，直到 PND140。小鼠在其一生（妊娠至成年）期间均喂食 CAS，用作对照（CAS 后代）。与 CAS 后代相比，SPI 后代的主动脉窦动脉粥样硬化病变减少。 CAS 子代或母鼠的总血清胆固醇水平与 SPI 子代的水平相当，这表明替代机制有助于母体 SPI 饮食的动脉粥样硬化保护作用。 SPI 后代的主动脉 VCAM-1、MCP-1 和 TNF-α 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，来自 SPI 后代的 CD4+ T 细胞显示 IFN-γ 表达 (Th1) 减少，而 IL-10 (Th2/Treg) 和 IL-13 (Th2) 表达增加。 DNA 甲基化分析显示，SPI 后代中抗炎 T 细胞相关基因（例如 Gata3 和 Il13 启动子区域）甲基化程度较低。这些发现表明，抗炎巨噬细胞和 T 细胞反应可能有助于 SPI 后代的动脉粥样硬化保护作用。我们的研究结果表明，妊娠期和哺乳期大豆饮食暴露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。
Maternal hypercholesterolemia has been implicated in the 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 were 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 genes such as Gata3 and Il13 promoter regions were hypomethylated in SPI-offspring. These findings suggest that anti-inflammatory macrophage and T cell response could 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.
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DOI：
10.1161/01.atv.0000282193.31936.fd
发表时间：
2007-10-01
影响因子：
8.7
作者：
Alkemade, Fanneke E.;Gittenberger-de Groot, Adriana C.;DeRuiter, Marco C.
通讯作者：
DeRuiter, Marco C.
影响因子：
15.9
作者：
Koltsova, Ekaterina K.;Garcia, Zacarias;Ley, Klaus
通讯作者：
Ley, Klaus
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
影响因子：
4.2
作者：
Day, JK;Bauer, AM;Lubahn, DB
通讯作者：
Lubahn, DB
影响因子：
8.7
作者：
Laukkanen, MO;Mannermaa, S;Ylä-Herttuala, S
通讯作者：
Ylä-Herttuala, S