Downregulating osteopontin reduces angiotensin II-induced inflammatory activation in vascular smooth muscle cells.
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 NFkappaB and activator protein-1 (AP-1), and the release of interleukin-6 (IL-6) and IL-1beta.


RESULTS
OPN was knocked down effectively in OPN RNAi group. Inflammatory activations, such as NFkappaB 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.
Yin
B L
BL
Department of Cardiovascular Surgery, The Second Xiang Ya Hospital of Central South University, HuNan, People's Republic of China.
Hao
H
H
Wang
Y Y
YY
Jiang
Y J
YJ
Xue
S
S
D000804:Angiotensin II / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D053495:Osteopontin; D000804:Angiotensin II