洪华山+郑乐民:肠道细菌产的TMAO或促进血管老化
创作:szx 审核:szx 2018年01月30日
  • 分析对比年轻人(18-44岁)及老年人(65岁以上)、不同年龄的SAMP8及SAMR1小鼠模型的血浆氧化三甲胺(TMAO)水平;
  • 在人类及小鼠中,循环TMAO水平均随着年龄增加而升高;
  • TMAO处理SAMR1小鼠16周,可引起血管老化,并加速SAMP8小鼠中的血管老化过程;
  • 体外实验发现,TMAO处理可引起人脐静脉内皮细胞(HUVEC)的衰老,减少细胞增殖,增加衰老标记物的表达,抑制细胞迁移;
  • 在体外及体内,TMAO均可抑制SIRT1的表达,增加氧化应激。
主编推荐语
mildbreeze
这是福建医科大学附属协和医院洪华山教授和北京大学医学部郑乐民教授(博士毕业于美国克利夫兰医学中心)合作发表在Free Radical Biology and Medicine[IF:5.606]的一项重要研究,发现不管是在人还是小鼠中,老年个体血液中氧化三甲胺(TMAO)的水平都比较高,且通过体内外实验,都初步证明TMAO可能促进内皮细胞衰老及血管老化。很值得关注的研究,特别推荐给大家。
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Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress

肠道菌群代谢产物氧化三甲胺通过氧化应激促进内皮细胞衰老及血管老化

10.1016/j.freeradbiomed.2018.01.007

2018-01-08, Article

Abstract & Authors:展开

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Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥ 65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1) models. We found that circulating TMAO increased with age both in humans and mice. Next, we observed that a TMAO treatment for 16 weeks induced vascular aging in SAMR1 mice and accelerated the process in SAMP8 mice, as measured by an upregulation of senescence markers including senescence-associated β-galactosidase (SA-β-gal), p53, and p21, vascular dysfunction and remodeling. In vitro, we demonstrated that prolonged TMAO treatment induced senescence in human umbilical vein endothelial cells (HUVECs), characterized by reduced cell proliferation, increased expressions of senescence markers, stagnate G0/G1, and impaired cell migration. Furthermore, TMAO suppressed sirtuin 1 (SIRT1) expression and increased oxidative stress both in vivo and in vitro and then activated the p53/p21/Rb pathway resulting in increased p53, acetylation of p53, p21, and decreased CDK2, cyclinE1, and phosphorylation of Rb. In summary, these data suggest that elevated circulating TMAO during the aging process may deteriorate EC senescence and vascular aging, which is probably associated with repression of SIRT1 expression and increased oxidative stress, and, thus, the activation of the p53/p21/Rb pathway.

First Authors:
Yilang Ke,Dang Li

Correspondence Authors:
Lemin Zheng,Huashan Hong

All Authors:
Yilang Ke,Dang Li,Mingming Zhao,Changjie Liu,Jia Liu,Aiping Zeng,Xiaoyun Shi,Si Cheng,Bing Pan,Lemin Zheng,Huashan Hong

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