Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.
Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.
复制标题
母体高脂饮食通过表观遗传学调节IRF8介导的骨细胞状巨噬细胞分化来促进成人后代的腹部主动脉瘤扩展。
DOI：
10.3390/cells10092224
复制
发表时间：
2021-08-27
期刊：
影响因子：
6
通讯作者：
Matoba S
中科院分区：
文献类型：
--
作者：
Saburi M;Yamada H;Wada N;Motoyama S;Sugimoto T;Kubota H;Miyawaki D;Wakana N;Kami D;Ogata T;Matoba S
母体高脂肪饮食（HFD）调节成年后代血管重塑。在这里，我们研究了母体HFD对腹主动脉瘤（AAA）发展的影响。雌性野生型小鼠分别饲喂HFD和正常饮食（ND）。用氯化钙诱导8周龄幼犬AAA。hfd饲喂的雄性后代与nd饲喂的雄性后代相比，AAA值显著增大。O-HFD中抗酒石酸磷酸酯（TRAP）和基质金属蛋白酶（MMP）活性阳性染色细胞显著增加。破骨细胞发生的药物抑制消除了O-HFD中夸大的AAA发展。体外肿瘤坏死因子-α-诱导的骨髓源性巨噬细胞的破骨细胞样分化在O-HFD中显示出更高的trap阳性细胞数量和破骨细胞特异性基因表达。与O-HFD中活化T细胞核因子1 （NFATc1）表达增加一致，转录抑制因子干扰素调节因子8 （IRF8）核蛋白表达明显降低，启动子区H3K27me3标记显著增加。zeste homolog 2 inhibitor的增强剂处理恢复了IRF8的表达，导致两组之间NFATc1和TRAP的表达没有差异。我们的研究结果表明，母体HFD增加了AAA的扩张，并伴随着过度的破骨细胞样巨噬细胞的积累，这表明巨噬细胞可能通过表观遗传重编程而扭曲。
Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.
登录
查看更多内容
影响因子：
16.6
作者：
通讯作者：
--
年龄相关的 Sirtuin 1 血管平滑肌减少与血管衰老和炎症与腹主动脉瘤有关
影响因子：
20.1
作者：
Chen HZ;Wang F;Gao P;Pei JF;Liu Y;Xu TT;Tang X;Fu WY;Lu J;Yan YF;Wang XM;Han L;Zhang ZQ;Zhang R;Zou MH;Liu DP
通讯作者：
Liu DP
DOI：
10.4049/jimmunol.1501466
发表时间：
2016-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fang C;Qiao Y;Mun SH;Lee MJ;Murata K;Bae S;Zhao B;Park-Min KH;Ivashkiv LB
通讯作者：
Ivashkiv LB
影响因子：
15.3
作者：
Asagiri, M;Sato, K;Takayanagi, H
通讯作者：
Takayanagi, H
影响因子：
5.2
作者：
Ivashkiv LB;Zhao B;Park-Min KH;Takami M
通讯作者：
Takami M