Interferon regulatory factor 1 attenuates vascular remodeling; roles of angiotensin II type 2 receptor.
We previously reported interferon regulatory factor (IRF) 1 plays physiological roles in "growth"-regulated angiotensin II type 2 (AT2) receptor expression in fibroblasts. Here, we investigated whether IRF-1 is involved in attenuation of vascular remodeling in association with AT2receptor upregulation. Neointimal area in injured artery after 14 days of cuff placement was significantly increased in IRF-1 knockout mice (IRF-1KO) and AT2receptor knockout mice (AT2KO) compared with wild-type mice (WT: C57BL/6J). Treatment with compound 21 attenuated neointima formation in both WT and IRF-1KO. AT2receptor mRNA expression after 7 days of cuff placement was significantly decreased in IRF-1KO compared with WT; however, IRF-1 expression did not differ between AT2KO and WT. Apoptotic changes in injured artery after 14 days of cuff placement were significantly attenuated in IRF-1KO, with a decrease in interleukin-1β-converting enzyme and inducible nitric oxide synthase mRNA levels. These results indicate IRF-1 is one of the key transcriptional factors for the prevention of neointimal formation involving AT2receptors.
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Hirotomo
H
Nakaoka
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan. Electronic address: mmogi@m.ehime-u.ac.jp.
Masaki
M
Mogi
Department of Cardiology, Pulmonology, Hypertension and Nephrology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Jun
J
Suzuki
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Harumi
H
Kan-No
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Li-Juan
LJ
Min
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Jun
J
Iwanami
Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Tohon, Ehime, Japan.
Masatsugu
M
Horiuchi
D000818:Animals; D017209:Apoptosis; D001158:Arteries / Q000293:injuries / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058426:Neointima / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000502:physiology*
D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020170:Caspase 1
AT(2) receptor; IRF-1; cell proliferation; oxidative stress