Heart Failure Disturbs Gut-Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite.
Heart Failure Disturbs Gut-Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite.
复制标题
DOI：
10.3390/ijms21176161
复制
发表时间：
2020-08-26
影响因子：
5.6
通讯作者：
Ufnal M
中科院分区：
文献类型：
--
作者：
Drapala A;Szudzik M;Chabowski D;Mogilnicka I;Jaworska K;Kraszewska K;Samborowska E;Ufnal M
三甲胺（TMA）是肠道细菌的产物，由肝脏氧化为三甲胺-N-氧化物（TMAO）。临床证据表明，心血管疾病与血浆TMAO升高有关。然而，在理解这种关系的机制和分子水平上取得的进展很少。本研究探讨了自发性高血压性心力衰竭（SHHF）大鼠血浆TMAO水平的影响机制。健康Wistar京都（WKY）和SHHF大鼠进行代谢、血流动力学、组织病理学和生化测量，包括紧密连接蛋白分析。使用超高效液相色谱-质谱法对粪便、血浆和尿液样品中的TMA和TMAO进行评价。SHHF表现出肠血屏障障碍，包括肠血流量减少、结肠粘膜厚度减少和紧密连接（如claudin 1和3以及闭合小带-1）的改变。与WKY相比，这与SHHF中TMA和TMAO的血浆水平显著更高以及TMA的肠道-血液渗透增加有关。肾功能或肝TMA氧化为TMAO在WKY和SHHF之间没有差异。总之，心力衰竭大鼠中血浆TMAO的增加是由于肠-血屏障的扰动和TMAO前体的肠-血通道增加，即，TMA。细菌代谢物的肠-血渗透增加可能是心血管病理学的标志物和介导物。
Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut–blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut–blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology.
登录
查看更多内容
影响因子：
1.2
作者：
Jaworska, Kinga;Huc, Tomasz;Ufnal, Marcin
通讯作者：
Ufnal, Marcin
DOI：
10.1056/nejmoa1109400
发表时间：
2013-04-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tang WH;Wang Z;Levison BS;Koeth RA;Britt EB;Fu X;Wu Y;Hazen SL
通讯作者：
Hazen SL
影响因子：
5.7
作者：
Suzuki, Toru;Heaney, Liam M.;Ng, Leong L.
通讯作者：
Ng, Leong L.
影响因子：
5.6
作者：
Querio, Giulia;Antoniotti, Susanna;Gallo, Maria Pia
通讯作者：
Gallo, Maria Pia
影响因子：
29.4
作者：
Tamura, Atsushi;Kitano, Yuka;Tsukita, Sachiko
通讯作者：
Tsukita, Sachiko