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

Original articles

Jing Zhao¹  Xiaoming Pang¹  Shouzhu Xu¹  Jingjing Zhao¹  Juntian Liu¹  Xiaolu Zhang² 

[1] Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, China;Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an, China;Department of Basic Medicine, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China;

关键词: aldosterone;    atherosclerosis;    C-reactive protein;    eplerenone;    inflammation;   

DOI  :  10.1177/1721727X17735261

 received in 2017-05-02, accepted in 2017-08-22,  发布年份 2017

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© The Author(s) 2017

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