Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy.
Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy.
复制标题
醛固酮通过抑制 AMPK 介导的自噬增强高磷酸盐诱导的血管钙化
DOI：
10.1111/jcmm.15813
复制
发表时间：
2020-12
影响因子：
5.3
通讯作者：
Liu PM
中科院分区：
文献类型：
--
作者：
Gao JW;He WB;Xie CM;Gao M;Feng LY;Liu ZY;Wang JF;Huang H;Liu PM
目前尚不清楚是否需要高无机磷(PI)诱导的钙化，以及自噬在醛固酮(ALDO)促进血管钙化(VC)和血管平滑肌细胞(VSMC)成骨分化中所起的作用。在本研究中，我们发现，只有在高PI存在的情况下，Aldo才能在体内和体外促进血管内皮细胞，同时增加VSMC成骨蛋白(BMP2、Runx2和Ocn)的表达，降低VSMC收缩蛋白(α-SMA、SM22α和Smothelin)的表达。然而，这些作用可被盐皮质激素受体抑制剂螺内酯阻断。此外，Aldo对VSMC钙化的刺激作用可被自噬抑制剂3-MA进一步加速，并被自噬诱导剂雷帕霉素所拮抗。此外，化合物C抑制一磷酸腺苷活化蛋白激酶(AMPK)可减弱Aldo/MR增强的Vc。这些结果表明，Aldo通过MR介导的信号通路促进高PI诱导的VSMC成骨表型转换和钙化，其中涉及AMPK依赖的自噬，这为在不同环境中Aldo过度相关的VC提供了新的见解。
It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)‐enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α‐SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3‐MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate‐activated protein kinase (AMPK) by Compound C attenuated Aldo/MR‐enhanced VC. These results suggested that Aldo facilitates high Pi‐induced VSMC osteogenic phenotypic switch and calcification through MR‐mediated signalling pathways that involve AMPK‐dependent autophagy, which provided new insights into Aldo excess‐associated VC in various settings.
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DOI：
10.1042/bj20121344
发表时间：
2013-05-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Salabei JK;Cummins TD;Singh M;Jones SP;Bhatnagar A;Hill BG
通讯作者：
Hill BG
影响因子：
9.3
作者：
Leopold JA
通讯作者：
Leopold JA
CDK9-CYCLIN T1复合物通过诱导转录因子CHOP的表达来介导饱和脂肪酸诱导的血管钙化。
DOI：
10.1074/jbc.ra118.004706
发表时间：
2018-11-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shiozaki Y;Okamura K;Kohno S;Keenan AL;Williams K;Zhao X;Chick WS;Miyazaki-Anzai S;Miyazaki M
通讯作者：
Miyazaki M
影响因子：
40.5
作者：
Thompson, Bithika;Towler, Dwight A.
通讯作者：
Towler, Dwight A.
影响因子：
9.3
作者：
Ferrario CM;Mullick AE
通讯作者：
Mullick AE