Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

Xiaochen Yuan; Naifeng Liu

doi:10.1016/j.jgg.2011.04.001

Volume 38 Issue 5

May 2011

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Article Navigation > Journal of Genetics and Genomics > 2011 > 38(5): 193-200

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Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

doi: 10.1016/j.jgg.2011.04.001

Xiaochen Yuan^{a, b},
Naifeng Liu^a

a
Department of Cardiology, Institute for Cardiovascular Medicine, Zhongda Hospital of Southeast University, Nanjing 210009, China
b
Department of Cardiology, Institute for Cardiovascular Medicine of Southeast University, the First People’s Hospital of Yangzhou, Yangzhou 225001, China

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Corresponding author: E-mail address: yz_yxc@sohu.com (Naifeng Liu)
Received Date: 2010-11-03
Accepted Date: 2011-04-02
Rev Recd Date: 2011-03-16

Available Online: 2011-04-15

Publish Date: 2011-05-20

Abstract

Abstract

Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting, respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARγ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). The ERK kinase inhibitor, U0126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERK1/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARγ pathways. Our findings suggested pioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.
- AGEs,
- PPARγ,
- Pioglitazone,
- Plasminogen activator inhibitor-1

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References(32)

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