Angiotensin II increases expression of IP-10 and the renin-angiotensin system in endothelial cells.
Angiotensin II promotes vascular inflammation, which plays important roles in vascular injury. In this study, we found that angiotensin II-stimulated human endothelial cells increased the release of a CXC chemokine, IP-10, according to an antibody array. IP-10 expression was higher in the endothelium of coronary blood vessels in mice infused with angiotensin II than in control. Quantitative real-time PCR analysis revealed that angiotensin II significantly increased IP-10 mRNA expression compared to control. Pretreatment with valsartan, but not with PD123319, blocked angiotensin II-induced IP-10 mRNA expression. IP-10 levels in conditioned media detected by ELISA increased in response to angiotensin II compared to control, which was blocked by the pretreatment with valsartan. These data indicate that angiotensin II stimulates IP-10 production from endothelial cells via angiotensin II type 1 receptors. In endothelial cells, IP-10 significantly increased mRNA expression of renin, angiotensin-converting enzyme, and angiotensinogen. IP-10 also increased angiotensin II levels in conditioned media compared to control. Angiotensin II significantly increased mRNA expression of renin, angiotensin converting enzyme and angiotensinogen, which was blocked by neutralization of IP-10 with antibody in endothelial cells. IP-10 neutralization with antibody blocked angiotensin II-induced apoptosis and cell senescence in endothelial cells. These data indicate that IP-10 is involved not only in leukocyte-endothelial interaction but also in the circuit of endothelial renin-angiotensin system activation that potentially promotes atherosclerosis.
Ide
Noriko
N
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
Hirase
Tetsuaki
T
Nishimoto-Hazuku
Ai
A
Ikeda
Yuji
Y
Node
Koichi
K
D000804:Angiotensin II / Q000494:pharmacology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II