Abstract
The AT(2) receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model of vascular remodeling and compared the responses in wild-type (Agtr2(+)) and AT(2) receptor knockout (Agtr2(-)) mice. Polyethylene cuff placement on the femoral artery led to the vascular expression of cytokines, the transcriptional factor interferon regulatory factor-1 (IRF-1), and both the AT(1) and AT(2) receptors. Although the expressions of IRF-1 and AT(1) receptor were induced to comparable levels in both the Agtr2(+) and Agtr2(-) mice, the neointimal lesion size and the smooth muscle cell proliferation were twice greater in the Agtr2(-) than in the Agtr2(+) mouse. Correlated with this difference, AT(2) receptor expression was induced predominantly in the smooth muscle cells of Agtr2(+) mouse. These results demonstrate that the AT(2) receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Angiotensin Receptor Antagonists
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Animals
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Blood Pressure / physiology
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Cytokines / genetics
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DNA-Binding Proteins / genetics
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Female
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Femoral Artery / metabolism
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Femoral Artery / pathology
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Femoral Artery / physiopathology*
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Gene Expression Regulation
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Heart Rate / physiology
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Hemodynamics
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Imidazoles / pharmacology
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Inflammation / physiopathology*
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Interferon Regulatory Factor-1
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Interferon-gamma / genetics
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Interleukin-1 / genetics
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Interleukin-6 / genetics
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Male
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Mice
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Mice, Knockout
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Phosphoproteins / genetics
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Pyridines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Receptors, Angiotensin / genetics*
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Receptors, Angiotensin / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tunica Intima / drug effects
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Tunica Intima / metabolism
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Tunica Intima / pathology
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Tunica Media / drug effects
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Tunica Media / metabolism
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Tunica Media / pathology
Substances
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Angiotensin Receptor Antagonists
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Cytokines
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DNA-Binding Proteins
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Imidazoles
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Interferon Regulatory Factor-1
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Interleukin-1
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Interleukin-6
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Irf1 protein, mouse
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Phosphoproteins
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Pyridines
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RNA, Messenger
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Receptors, Angiotensin
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Tumor Necrosis Factor-alpha
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PD 123319
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Interferon-gamma