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Rosiglitazone inhibits angiotensin II-induced C-reactive protein production in human aortic endothelial cells through regulating AT1–ROS–MAPK signal pathway

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Abstract

Objective

Atherosclerosis is an inflammatory disease. As an inflammatory molecule, C-reactive protein (CRP) plays a direct role in atherogenesis. Our previous study confirmed that angiotensin II (Ang II) is capable of inducing CRP generation in human aortic endothelial cells (HAECs). The present study observed the effect of rosiglitazone on Ang II-induced CRP expression in HAECs and molecular mechanisms.

Methods

HAECs were cultured, and Ang II (10−6 M) was used as a stimulant for the generation of CRP and reactive oxygen species (ROS). HAECs were preincubated with rosiglitazone at 1, 10, 100 µM for 18 h prior to the stimulation. mRNA and protein expressions were identified by reverse transcription polymerase chain reaction and Western blot, respectively. ROS production was observed by a fluorescence microscope.

Results

Pretreatment of HAECs with rosiglitazone prior to Ang II stimulation markedly downregulated Ang II-induced mRNA and protein expressions of CRP (maximal inhibition of 55.2 and 99.1 %, P < 0.001 vs. Ang II alone) and AT1 (maximal inhibition of 66.4 and 90.5 %, P < 0.001 vs. Ang II alone) in a concentration-dependent manner, inhibited Ang II-stimulated ROS production (P < 0.01 vs. Ang II alone), and attenuated Ang II-induced phosphorylation of ERK1/2 and JNK (P < 0.001 vs. Ang II alone). Meanwhile, AT1 receptor blocker losartan also reduced Ang II-stimulated ROS generation in HAECs (P < 0.001 vs. Ang II alone).

Conclusions

Rosiglitazone at the concentrations used in the present experiment is able to inhibit Ang II-induced CRP generation in HAECs by regulating AT1–ROS–MAPK signal pathway. These results strengthen our understanding of the anti-inflammatory and anti-atherosclerotic effects of rosiglitazone.

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Acknowledgments

This work was supported by the Doctoral Fund of the Ministry of Education of China (No. 20100201110053).

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Authors and Affiliations

  1. Department of Pharmacology, Xi’an Jiaotong University School of Medicine, 76 West Yanta Road, Postbox 58, Xi’an, 710061, People’s Republic of China

    Chun-Jie Han, Jun-Tian Liu, Ming Li, Xiao-Ming Pang, Jun-Jun Mao & Xiao-Fang Liu

  2. Department of Pharmacology, Shaanxi Institute for Food and Drug Control, Xi’an, People’s Republic of China

    Chun-Jie Han

  3. Nursing Department, Xi’an Medical University, Xi’an, People’s Republic of China

    Mu Cui

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  1. Chun-Jie Han
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  2. Jun-Tian Liu
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Correspondence to Jun-Tian Liu.

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Responsible Editor: Ikuo Morita.

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Han, CJ., Liu, JT., Li, M. et al. Rosiglitazone inhibits angiotensin II-induced C-reactive protein production in human aortic endothelial cells through regulating AT1–ROS–MAPK signal pathway. Inflamm. Res. 61, 1031–1037 (2012). https://doi.org/10.1007/s00011-012-0496-9

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  • DOI: https://doi.org/10.1007/s00011-012-0496-9

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