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Activation of ERK5 in angiotensin II-induced hypertrophy of human aortic smooth muscle cells

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Abstract

Extracellular signal-regulated kinase 5 (ERK5), a recently discovered mitogen-activated protein kinase (MAPK), plays a key role in the development and pathogenesis of cardiovascular disease. In order to clarify the pathophysiological significance of ERK5 in vascular remodeling, we investigated ERK5 phosphorylation in hypertrophy of human aortic smooth muscle cells (HASMCs) induced by angiotensin II (Ang II). The AT1 receptor was involved in Ang II-induced ERK5 activity. Hypertrophy was detected by the measurement of protein synthesis with [3H]-Leu incorporation in cultured HASMCs. Ang II rapidly induced phosphorylation of ERK5 at Thr218/Tyr220 residues in a time- and dose-dependent manner. Activation of myocyte enhancer factor-2C (MEF2C) by ERK5 was inhibited by PD98059. Transfecting HASMCs with small interfering RNA (siRNA) to silence ERK5 inhibited Ang II-induced cell hypertrophy. Thus, ERK5 phosphorylation contributes to MEF2C activation and subsequent HASMC hypertrophy induced by Ang II, for a novel molecular mechanism in cardiovascular diseases induced by Ang II.

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Acknowledgments

We gratefully acknowledge the technical assistance from Dr. Jinbo Feng, and Dr. Guanghui Liu in histopathological and molecular biological analysis. This study was supported by the National 973 Basic Research Program of China (No.2007CB512003) and Natural Fund of Shandong Province (Y2007C012).

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Authors and Affiliations

  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Wenhua Xi Road, 250012, Jinan, Shandong, People’s Republic of China

    Zhuo Zhao, Jing Geng, Zhiming Ge, Yun Zhang & Weiqiang Kang

  2. Department of Cardiology, Shandong Provincial Chest Hospital, Huayuan Road, 250012, Jinan, Shandong, People’s Republic of China

    Wei Wang

  3. Department of Cardiology, Jinan Central Hospital, Jiefang Road, Jinan, Shandong, 250021, China

    Zhuo Zhao

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  1. Zhuo Zhao
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  2. Jing Geng
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  3. Zhiming Ge
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  4. Wei Wang
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  5. Yun Zhang
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Correspondence to Weiqiang Kang.

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Zhuo Zhao and Jing Geng contributed equally to this work.

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Zhao, Z., Geng, J., Ge, Z. et al. Activation of ERK5 in angiotensin II-induced hypertrophy of human aortic smooth muscle cells. Mol Cell Biochem 322, 171–178 (2009). https://doi.org/10.1007/s11010-008-9954-7

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