Abstract
Background
Atherosclerosis is an inflammatory disease in the vessel. As an inflammatory cytokine,
C-reactive protein (CRP) participates in atherogenesis. Although angiotensin II (AngII)
is known to evoke inflammatory response in vascular endothelial cells (VECs), there
is no direct evidence to demonstrate the proinflammatory effect of AngII on VECs through
CRP. The present study focused on effect of AngII on CRP expression and the signal
pathway in human aortic endothelial cells (HAECs).
Methods and results
mRNA and protein expression was identified by RT-PCR and Western blot, respectively.
Reactive oxygen species (ROS) were observed by a fluorescence microscope. The results
showed that AngII significantly increased mRNA and protein expression of CRP in HAECs
in time- and concentration-dependent ways. Anti-IL-1β and anti-IL-6 neutralizing antibodies
did not affect AngII-induced CRP expression. Losartan reduced AngII-induced CRP expression
in mRNA and protein levels in HAECs. Losartan and TIFA decreased AngII-stimulated
ROS generation, and antioxidant NAC completely abolished AngII-induced CRP expression
in HAECs. The further study indicated that losartan, NAC, PD98059, SP600125 significantly
inhibited ERK1/2 and JNK phosphorylation, and PD98059, SP600125, PDTC completely antagonized
AngII-induced CRP expression in HAECs.
Conclusions
The present study demonstrates that AngII has ability to induce CRP expression in
HAECs through AT1-ROS-ERK1/2 and JNK-NF-κB signal pathway, which strengthens understanding of the proinflammatory
and proathroscerotic actions of AngII.
Keywords
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Article info
Publication history
Published online: June 10, 2010
Accepted:
May 11,
2010
Received in revised form:
April 21,
2010
Received:
March 14,
2010
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.