Novel Regulatory Effect of Angiotensin II Type 1 Receptor-Interacting Molecule on Vascular Smooth Muscle Cells

• DOI: 10.1161/hypertensionaha.107.096115
• Publication Date: 2007-09-18T01:09:46Z
• Authors: Koichi Azuma; Kouichi Tamura; Atsu-ichiro Shige...; Hiromichi Wakui; Shin-ichiro Masuda; Yuko Tsurumi-Ikeya; Yutaka Tanaka; Masashi Sakai; Miyuki Matsuda; Tatsuo Hashimoto; Tomoaki Ishigami; Marco Lopez-Ilasaca; Satoshi Umemura
• Keywords: Colocalization

We have recently cloned a novel molecule that interacts with the angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP). In this study, we tested hypothesis ATRAP modulates II-induced responses in vascular smooth muscle cells. The results of immunoprecipitation and bioluminescence resonance energy transfer assay demonstrated direct interaction between AT1R at baseline showed enhanced these proteins >2-fold. immunofluorescence analysis also >65% constitutively colocalized an endosome marker. Although only 36% baseline, colocalization molecules made 92% colocalize on quantitative fluorescence analysis. Overexpression by adenoviral decreased cell surface number from 4.33 to 2.13 fmol/10 6 cells 3.04 1.26 even after removal II. suppressed II-mediated increases c-fos gene transcription transforming growth factor-β production. Furthermore, suppression was accompanied inhibition activation 5-bromodeoxyuridine incorporation. Finally, knockdown small-interference RNA activated expression, which effectively inhibited valsartan, AT1R-specific antagonist. These indicate promotes internalization attenuates c-fos-transforming pathway proliferative response cells, suggesting strategy inhibit fibrosis remodeling through specific blockade signaling.