Abstract.
Objective:
Atherosclerosis is considered as a chronic inflammatory response in arterial blood vessels. The function of osteopontin (OPN), a proinflammatory cytokine, in the Ang II-induced inflammatory activation in vascular smooth muscle cells (VSMCs) remains poorly understood.
Methods:
In the present study, the role of OPN was investigated by knocking down OPN using small interfering RNA (siRNA). VSMCs from human saphenous vein were divided into three groups according to RNAi treatment: OPN siRNA group, sham (un-transfected) treated group, and control siRNA group. RNAi effect was investigated by real time PCR, western blotting analysis and ELISA. Then all groups were stimulated with Ang II. The inflammatory activation was assessed by determining the activation of NFκB and activator protein-1 (AP-1), and the release of interleukin-6 (IL-6) and IL-1β.
Results:
OPN was knocked down effectively in OPN RNAi group. Inflammatory activations, such as NFκB and AP-1 activation and IL-6 accumulation, were induced by Ang II in sham treated group and control siRNA group. However, it was abolished in OPN siRNA group by the downregulation of OPN compared to sham treated group and control siRNA group.
Conclusions:
This result suggested that OPN plays an important role in Ang II-induced inflammatory activation in VSMCs. The finding further supports OPN as a potential target for atherosclerotic therapy.
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Received 21 February 2008; returned for revision 6 May 2008; received from final revision 16 May 2008; accepted by S. Stimpson 21 August 2008
The first three authors contributed equally to this work.
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Yin, B.L., Hao, H., Wang, Y.Y. et al. Downregulating osteopontin reduces angiotensin II-induced inflammatory activation in vascular smooth muscle cells. Inflamm. Res. 58, 67–73 (2009). https://doi.org/10.1007/s00011-009-8034-0
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DOI: https://doi.org/10.1007/s00011-009-8034-0