Inflammation influences vascular remodeling through AT2receptor expression and signaling

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Abstract
Akishita, Masahiro, Masatsugu Horiuchi, Hiroyuki Yamada, Lunan Zhang, Gotaro Shirakami, Kouichi Tamura, Yasuyoshi Ouchi, and Victor J. Dzau. Inflammation influences vascular remodeling through AT2receptor expression and signaling. Physiol. Genomics 2: 13–20, 2000.—The AT2receptor, 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 AT2receptor 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 AT1and AT2receptors. Although the expressions of IRF-1 and AT1receptor 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, AT2receptor expression was induced predominantly in the smooth muscle cells of Agtr2+mouse. These results demonstrate that the AT2receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.