Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis.
Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis.
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胆汁酸核受体FXR和G蛋白偶联受体TGR5的双重激活可保护小鼠免受动脉粥样硬化。
DOI：
10.1371/journal.pone.0108270
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Miyazaki M
中科院分区：
文献类型：
--
作者：
Miyazaki-Anzai S;Masuda M;Levi M;Keenan AL;Miyazaki M
Bile acid signaling is a critical regulator of glucose and energy metabolism, mainly through the nuclear receptor FXR and the G protein-coupled receptor TGR. The purpose of the present study was to investigate whether dual activation of FXR and TGR5 plays a significant role in the prevention of atherosclerosis progression. To evaluate the effects of bile acid signaling in atherogenesis, ApoE−/− mice and LDLR−/− mice were treated with an FXR/TGR5 dual agonist (INT-767). INT-767 treatment drastically reduced serum cholesterol levels. INT-767 treatment significantly reduced atherosclerotic plaque formation in both ApoE−/− and LDLR−/− mice. INT-767 decreased the expression of pro-inflammatory cytokines and chemokines in the aortas of ApoE−/− mice through the inactivation of NF-κB. In addition, J774 macrophages treated with INT-767 had significantly lower levels of active NF-κB, resulting in cytokine production in response to LPS through a PKA dependent mechanism. This study demonstrates that concurrent activation of FXR and TGR5 attenuates atherosclerosis by reducing both circulating lipids and inflammation.
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DOI：
10.1111/j.1749-6632.2002.tb04326.x
发表时间：
2002-01-01
期刊：
PROTEIN KINASE A AND HUMAN DISEASE
影响因子：
--
作者：
Chin, KV;Yang, WL;Iacono, L
通讯作者：
Iacono, L
影响因子：
4.8
作者：
Miyazaki, M;Kim, YC;Ntambi, JM
通讯作者：
Ntambi, JM
影响因子：
5.3
作者：
Ceryak, S;Bouscarel, B;Fromm, H
通讯作者：
Fromm, H
影响因子：
20.1
作者：
Miyazaki-Anzai S;Levi M;Kratzer A;Ting TC;Lewis LB;Miyazaki M
通讯作者：
Miyazaki M
影响因子：
4.8
作者：
McMahan, Rachel H.;Wang, Xiaoxin X.;Rosen, Hugo R.
通讯作者：
Rosen, Hugo R.