Maternal exposure to soy diet reduces atheroma in hyperlipidemic F1 offspring mice by promoting macrophage and T cell anti-inflammatory responses. (November 2020)

• Record Type: Journal Article
• Authors: Burris, Ramona L.; Vick, Sarah C.; Popovic, Branimir; Fraungruber, Pamelia E.; Nagarajan, Shanmugam
• Is Part Of: Atherosclerosis. Volume 313(2020)
• Page Start: 26
• Page End: 34
• Publication Date: 2020-11
• Subjects: Gestation -- Inflammation -- Maternal hypercholesterolemia -- Soy protein -- Atherosclerosis; Apoe−/− apolipoprotein E knockout -- CAS casein -- CVD cardiovascular disease -- MCP-1 monocyte chemoattractant protein-1 -- PND postnatal day -- SPI isoflavone-free soy protein isolate -- TNF-α tumor necrosis factor-α -- VCAM-1 vascular cell adhesion molecule-1; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2020.09.018
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: 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. Method: 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). Results: 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. Conclusions: 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. Graphical abstract: Image 1 Highlights: Maternal hypercholesterolemia has been implicated in earlier onset of atherosclerotic lesions in neonatal offspring. We investigated if prenatal exposure to soy diet attenuates the development of atherosclerosis in F1 offspring. While maternal soy protein isolate (SPI) diet did not affect total cholesterol, it did reduce atherosclerotic lesions in SPI-offspring. VCAM-1, MCP-1, and TNF-alpha expression is reduced in SPI-offspring. In SPI-offspring, expression of anti-inflammatory cytokines by T cells was increased.