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


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-1beta 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 AT(1)-ROS-ERK1/2 and JNK-NF-kappaB signal pathway, which strengthens understanding of the proinflammatory and proathroscerotic actions of AngII.
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
Chunjie
C
Han
Juntian
J
Liu
Xiaofang
X
Liu
Ming
M
Li
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D050197:Atherosclerosis / Q000201:enzymology / Q000276:immunology; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002097:C-Reactive Protein; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3