The Physiology and Pathophysiology of a Novel Angiotensin Receptor-binding Protein ATRAP/Agtrap

Shin-ichiro      Masuda; Satoshi      Umemura; Akio      Yamashita; Yasuo      Tokita; Yoshiyuki      Toya; Miyuki      Matsuda; Yuko      Tsurumi-Ikeya; Yuichi      Koide; Atsu-ichiro      Shigenaga; Koichi      Azuma; Kouichi      Tamura; Kazushi      Uneda; Sona      Haku; Tomohiko      Kanaoka; Kengo      Azushima; Masato      Ohsawa; Toru      Dejima; Akinobu      Maeda; Hiromichi      Wakui

doi:10.2174/1381612811319170010

Abstract

The Ang II type 1 receptor (AT1R)-associated protein (ATRAP/Agtrap) is a molecule specifically interacting with the carboxyl- terminal domain of AT1R. The results of in vitro studies showed that ATRAP suppresses Ang II-mediated pathological responses in cardiovascular cells by promoting AT1R internalization. With respect to the tissue distribution and regulation of ATRAP expression in vivo, ATRAP is broadly expressed in many tissues as is AT1R. Accumulating evidence indicates that a tissue-specific regulatory balancing of ATRAP and AT1R expression may be involved in the modulation of AT1R signaling at local tissue sites and also in the pathophysiology of hypertension and its associated end-organ injury. Furthermore, the activation of ATRAP in transgenic-models inhibited inflammatory vascular remodeling and cardiac hypertrophy in response to Ang II stimulation. These results suggest the clinical potential benefit of an ATRAP activation strategy in the treatment of hypertension and related organ injury.

Keywords: Gene expression/regulation, hypertension, receptor internalization, receptor signaling, renin-angiotensin system, target organ injury.

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