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Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells

      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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