Abstract 17365: Activation of Angiotensin II Type 1 Receptor-associated Protein Suppresses Vascular Hypertrophy And Oxidative Stress in Angiotensin II Mediated Hypertension
Backgrounds: We previously cloned a molecule interacting with Ang II type 1 receptor, which we named ATRAP (for Ang II type 1 receptor-associated protein). Previous in vitro studies showed that ATRAP promotes constitutive internalization of the Ang II type 1 receptor and further attenuates Ang II-mediated hypertrophic responses in cardiovascular cells. Increased reactive oxygen species (ROS) are implicated in several vascular pathological states associated with vascular hypertrophy.
Objective: The present study was designed to investigate the putative functional role of ATRAP in vascular hypertrophy and oxidative stress in hypertension in vivo.
Methods & Results: We first examined the effect of Ang II infusion on aortic hypertrophy and NADPH oxidase components expression in the aorta of C57BL/6J wild-type mice. The Ang II treatment promoted vascular hypertrophy in aorta, with a concomitant and significant increase in the expression of aortic NADPH oxidase components. We next generated transgenic mice expressing ATRAP in tissues including aorta under control of the β-actin promoter. Systolic blood pressure did not differ between wild-type mice and ATRAP transgenic mice at baseline and comparably and significantly increased both in wild-type mice and in ATRAP transgenic mice in response to Ang II infusion. However, in the aorta of ATRAP transgenic mice, the Ang II hypertension-mediated development of vascular hypertrophy and activation of NADPH oxidase components were significantly suppressed.
Conclusion: These results demonstrate that activation of ATRAP at local tissue sites including aorta efficiently inhibits the vascular hypertrophy and oxidative stress provoked by Ang II-mediated hypertension, thereby suggesting ATRAP to be a novel therapeutic target in vascular disease.
- © 2013 by American Heart Association, Inc.