Maternal hypercholesterolemia exacerbates atherosclerosis lesions in female offspring through potentiating macrophage polarization toward an inflammatory M1 phenotype

Maternal hypercholesterolemia induces early onset of cardiovascular diseases in offspring; however, its underlying mechanism remains poorly understood. We hypothesized that maternal hypercholesterolemia increases offspring susceptibility to atherosclerosis in adulthood through developmental modifica...

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Bibliographic Details
Published in:The Journal of nutritional biochemistry 2021-04, Vol.90, p.108575-108575, Article 108575
Main Authors: Chen, Sin-Yu, Chen, Yi-Zhen, Lee, Yi-Jing, Jiang, Chung-Lin, Lu, Shao-Chun, Lin, Fu-Jung
Format: Article
Language:English
Subjects:
Apolipoprotein E
Atherosclerosis
Hypercholesterolemia
Inflammation
Macrophage
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Summary:Maternal hypercholesterolemia induces early onset of cardiovascular diseases in offspring; however, its underlying mechanism remains poorly understood. We hypothesized that maternal hypercholesterolemia increases offspring susceptibility to atherosclerosis in adulthood through developmental modifications of macrophages. Female apolipoprotein E (ApoE)-deficient mice were fed a Western-type diet (WD) or a control diet (CD) prior to and throughout gestation and lactation. The offspring were all fed a WD after weaning. Sixteen-week-old female offspring of WD-fed dams showed a significant increase in atherosclerotic lesions of the aorta and aortic root compared with those of CD-fed dams. This effect was associated with increased macrophage accumulation within lesions, macrophage inflammation and an increase in circulating Ly6Chigh monocyte and F4/80 macrophage counts. We further evidenced that in utero WD exposure promoted macrophage polarization toward the M1 phenotype by elevating M1 markers (Cd86, Inos/Nos2) without affecting M2 markers (Cd206, Arg1). Proinflammatory cytokine synthesis was also enhanced in response to LPS. Finally, maternal WD intake strongly inhibited the macrophage expression of Pparg and Lxra, which was associated with aberrant DNA methylation of Lxra promoter. Our findings demonstrate that maternal hypercholesterolemia exacerbates atherosclerosis, in part by altering the epigenetic state of the macrophage genome of the offspring, imprinting gene expression, and changing macrophage polarization, which ultimately contributes to plaque macrophage burden. [Display omitted]
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2020.108575