Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway
Atherosclerosis is a chronic inflammatory disease in the vessel wall. As a representative inflammatory cytokine, C-reactive protein (CRP) participates in the formation and development of atherosclerosis. It is demonstrated that aldosterone induces CRP generation in vascular smooth muscle cells (VSMC...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-12-01
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| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/1721727X17735261 |
| _version_ | 1818619653604245504 |
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| author | Xiaolu Zhang Juntian Liu Xiaoming Pang Jingjing Zhao Shouzhu Xu Jing Zhao |
| author_facet | Xiaolu Zhang Juntian Liu Xiaoming Pang Jingjing Zhao Shouzhu Xu Jing Zhao |
| author_sort | Xiaolu Zhang |
| collection | DOAJ |
| description | Atherosclerosis is a chronic inflammatory disease in the vessel wall. As a representative inflammatory cytokine, C-reactive protein (CRP) participates in the formation and development of atherosclerosis. It is demonstrated that aldosterone induces CRP generation in vascular smooth muscle cells (VSMCs). This study explored the inhibitory effect of eplerenone on aldosterone-induced CRP expression in VSMCs and mechanism. In the in vitro experiments, rat VSMCs were cultured and aldosterone (10 nM) was used as a stimulant for CRP generation. VSMCs were pretreated with eplerenone for 1 h prior to the stimulation. Messenger RNA (mRNA) and protein expression were identified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively. The production of reactive oxygen species (ROS) was observed by a fluorescence microscope. In the in vivo experiment, a model of hyperaldosteronism was established by the subcutaneous administration of aldosterone to rats with the osmotic minipumps for 4 weeks. Serum aldosterone and CRP levels were determined with a radioimmunoassay and ELISA (enzyme-linked immunosorbent assay), respectively. The results showed that eplerenone inhibited aldosterone-induced mRNA and protein expression of CRP in VSMCs in vitro and in vivo, and decreased the circulating CRP level of hyperaldosteronism rats. Meanwhile, eplerenone reduced aldosterone-stimulated ROS generation and aldosterone-activated ERK1/2 phosphorylation in VSMCs. In summary, eplerenone inhibits aldosterone-induced CRP generation in VSMCs by regulating the MR-ROS-ERK1/2 signal pathway. These results provide new evidence for the potential anti-inflammatory effect of eplerenone. |
| first_indexed | 2024-12-16T17:40:54Z |
| format | Article |
| id | doaj.art-f8b237addb994deaa8e4e6db58b2f244 |
| institution | Directory Open Access Journal |
| issn | 1721-727X |
| language | English |
| last_indexed | 2024-12-16T17:40:54Z |
| publishDate | 2017-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-f8b237addb994deaa8e4e6db58b2f2442022-12-21T22:22:37ZengSAGE PublishingEuropean Journal of Inflammation1721-727X2017-12-011510.1177/1721727X17735261Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathwayXiaolu Zhang0Juntian Liu1Xiaoming Pang2Jingjing Zhao3Shouzhu Xu4Jing Zhao5Department of Basic Medicine, Hebei University of Traditional Chinese Medicine, Shijiazhuang, ChinaDepartment of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, ChinaAtherosclerosis is a chronic inflammatory disease in the vessel wall. As a representative inflammatory cytokine, C-reactive protein (CRP) participates in the formation and development of atherosclerosis. It is demonstrated that aldosterone induces CRP generation in vascular smooth muscle cells (VSMCs). This study explored the inhibitory effect of eplerenone on aldosterone-induced CRP expression in VSMCs and mechanism. In the in vitro experiments, rat VSMCs were cultured and aldosterone (10 nM) was used as a stimulant for CRP generation. VSMCs were pretreated with eplerenone for 1 h prior to the stimulation. Messenger RNA (mRNA) and protein expression were identified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively. The production of reactive oxygen species (ROS) was observed by a fluorescence microscope. In the in vivo experiment, a model of hyperaldosteronism was established by the subcutaneous administration of aldosterone to rats with the osmotic minipumps for 4 weeks. Serum aldosterone and CRP levels were determined with a radioimmunoassay and ELISA (enzyme-linked immunosorbent assay), respectively. The results showed that eplerenone inhibited aldosterone-induced mRNA and protein expression of CRP in VSMCs in vitro and in vivo, and decreased the circulating CRP level of hyperaldosteronism rats. Meanwhile, eplerenone reduced aldosterone-stimulated ROS generation and aldosterone-activated ERK1/2 phosphorylation in VSMCs. In summary, eplerenone inhibits aldosterone-induced CRP generation in VSMCs by regulating the MR-ROS-ERK1/2 signal pathway. These results provide new evidence for the potential anti-inflammatory effect of eplerenone.https://doi.org/10.1177/1721727X17735261 |
| spellingShingle | Xiaolu Zhang Juntian Liu Xiaoming Pang Jingjing Zhao Shouzhu Xu Jing Zhao Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway European Journal of Inflammation |
| title | Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway |
| title_full | Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway |
| title_fullStr | Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway |
| title_full_unstemmed | Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway |
| title_short | Eplerenone inhibits aldosterone-induced CRP generation in rat vascular smooth muscle cells by regulating the MR-ROS-ERK1/2 signal pathway |
| title_sort | eplerenone inhibits aldosterone induced crp generation in rat vascular smooth muscle cells by regulating the mr ros erk1 2 signal pathway |
| url | https://doi.org/10.1177/1721727X17735261 |
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