Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats

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概要

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• Advanced glycation end products (AGEs) have been shown to induce the proliferation of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis and diabetes. In the present study, we investigated the effects of pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist, on AGE-induced rat VSMC growth and the underlying mechanism. In cultured rat VSMCs, AGE treatment induced VSMC proliferation in time- and dose-dependent manner, while down-regulated the expression of PPARγ. Pretreatment of pioglitazone not only prevented the down-regulation of PPARγ, but inhibited VSMC proliferation and prevented S-phase entry of cell via a G0–G1 block in the presence of AGEs. Western blotting analysis showed that AGE treatment potentiated to activate extracelluar signal-regulated kinases (ERK1/2) by the induction of intracellular reactive oxygen species (ROS) production, since ROS scavenger N-acetyl-L-cysteine pretreatment significantly inhibited AGE-induced ERK1/2 activation. Further, pretreatment with either N-acetyl-L-cysteine or the inhibitor of ERK1/2 activation suppressed AGE-induced proliferation of VSMCs, suggesting a role of ROS/ERK1/2 signaling. Notably, we demonstrated that pretreatment of pioglitazone significantly attenuated AGE-induced ROS and ERK1/2 activation. Collectively, these results suggest that pioglitazone inhibits AGE-induced VSMC proliferation via increasing PPARγ expression and inhibiting ROS/ERK1/2 signaling pathway.

著者

• Zhao Pei

  Department Of Biology Tianjin Normal University

• Qin Jianhua

  Department Of Biotechnology Dalian Institute Of Chemical Physics Chinese Academy Of Sciences

• Yuan Xiaochen

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First Peo

• Zhang Zhengang

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First Peo

• Gong Kaizheng

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First Peo

• Liu Naifeng

  Department of Cardiology, Institute of Cardiovascular Medicine of Southeast University, Zhongda Hosp

• Zhao Pei

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou

• Qin Jianhua

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou

• Liu Naifeng

  Department of Cardiology, Institute of Cardiovascular Medicine of Southeast University, Zhongda Hospital of Southeast University

• Zhang Zhengang

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou

• Yuan Xiaochen

  Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou

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