Upregulation of Cyclooxygenase-2 by Motorcycle Exhaust Particulate-Induced Reactive Oxygen Species Enhances Rat Vascular Smooth Muscle Cell Proliferation

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• 作者：Huei-Ping Tzeng ; Rong Sen Yang ; Tzuu-Huei Ueng ; Shing-Hwa Liu
• 刊名：Chemical Research in Toxicology
• 出版年：2007
• 出版时间：August 2007
• 年：2007
• 卷：20
• 期：8
• 页码：1170 - 1176
• 全文大小：529K
• 年卷期：v.20,no.8(August 2007)
• ISSN：1520-5010

文摘

Long-term exposure to particulate air pollution has been implicated as a risk factor for cardiovascular disease and mortality. Short-term exposure has also been suggested to contribute to complications of atherosclerosis. Aberrant regulation of smooth muscle cell proliferation is thought to associate with the pathophysiology of vascular disorders such as atherosclerosis. In this study, we investigate the influence of organic extracts of motorcycle exhaust particulates (MEPE) on rat vascular smooth muscle cell (VSMC) proliferation and related regulation signaling. Exposure of VSMCs to MEPE (10–100 µg/mL) enhanced serum-induced VSMC proliferation. The expression of proliferating cell nuclear antigen (PCNA) was also enhanced in the presence of MEPE. VSMCs treated with MEPE induced the increase in the extent of cyclooxygenase (COX)-2 mRNA and protein expression and prostaglandin E₂ production, whereas the level of COX-1 protein was unchanged. Moreover, MEPE increased the production of reactive oxygen species (ROS) in VSMCs in a dose-dependent manner. MEPE could also trigger time-dependently extracellular signal-regulated kinase (ERK)1/2 phosphorylation in VSMCs, which was attenuated by antioxidants N-acetylcysteine (NAC) and pyrrolidinedithiocarbamate (PDTC). The level of translocation of nuclear factor (NF)-κB-p65 in the nuclei of VSMCs was also increased under MEPE exposure. The potentiating effect of MEPE on serum-induced VSMC proliferation could be abolished by COX-2 selective inhibitor NS-398, specific ERK inhibitor PD98059, and antioxidants NAC and PDTC. Taken together, these findings suggest that MEPE may contribute to the enhancement of the pathogenesis of cardiovascular diseases by augmenting proliferation of VSMCs through a ROS-regulated ERK1/2-activated COX-2 signaling pathway.