Inflammation influences vascular remodeling through AT2 receptor expression and signaling

Abstract

Akishita, Masahiro, Masatsugu Horiuchi, Hiroyuki Yamada, Lunan Zhang, Gotaro Shirakami, Kouichi Tamura, Yasuyoshi Ouchi, and Victor J. Dzau. Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol. Genomics 2: 13–20, 2000.—The AT2 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 AT2 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 AT1 and AT2 receptors. Although the expressions of IRF-1 and AT1 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, AT2 receptor expression was induced predominantly in the smooth muscle cells of Agtr2+ mouse. These results demonstrate that the AT2 receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.