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Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension.
Cardiovasc Res. 2013 Dec 01; 100(3):511-9.CR

Abstract

AIMS

Activation of tissue angiotensin II (Ang II) type 1 receptor (AT1R) plays an important role in the development of vascular remodelling. We have shown that the AT1R-associated protein (ATRAP/Agtrap), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent pathological activation of the tissue renin-angiotensin system. In this study, we investigated the effects of ATRAP on Ang II-induced vascular remodelling.

METHODS AND RESULTS

Transgenic (Tg) mice with a pattern of aortic vascular-dominant overexpression of ATRAP were obtained, and Ang II or vehicle was continuously infused into Tg and wild-type (Wt) mice via an osmotic minipump for 14 days. Although blood pressure of Ang II-infused Tg mice was comparable with that of Ang II-infused Wt mice, the Ang II-mediated development of aortic vascular hypertrophy was partially inhibited in Tg mice compared with Wt mice. In addition, Ang II-mediated up-regulation of vascular Nox4 and p22(phox), NADPH oxidase components, and 4-HNE, a marker of reactive oxygen species (ROS) generation, was significantly suppressed in Tg mice, with a concomitant inhibition of activation of aortic vascular p38MAPK and JNK by Ang II. This protection afforded by vascular ATRAP against Ang II-induced activation of NADPH oxidase is supported by in vitro experimental data using adenoviral transfer of recombinant ATRAP.

CONCLUSION

These results indicate that activation of aortic vascular ATRAP partially inhibits the Nox4/p22(phox)-ROS-p38MAPK/JNK pathway and pathological aortic hypertrophy provoked by Ang II-mediated hypertension, thereby suggesting ATRAP as a novel receptor-binding modulator of vascular pathophysiology.

Authors+Show Affiliations

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24189624

Citation

Wakui, Hiromichi, et al. "Activation of Angiotensin II Type 1 Receptor-associated Protein Exerts an Inhibitory Effect On Vascular Hypertrophy and Oxidative Stress in Angiotensin II-mediated Hypertension." Cardiovascular Research, vol. 100, no. 3, 2013, pp. 511-9.
Wakui H, Dejima T, Tamura K, et al. Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension. Cardiovasc Res. 2013;100(3):511-9.
Wakui, H., Dejima, T., Tamura, K., Uneda, K., Azuma, K., Maeda, A., Ohsawa, M., Kanaoka, T., Azushima, K., Kobayashi, R., Matsuda, M., Yamashita, A., & Umemura, S. (2013). Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension. Cardiovascular Research, 100(3), 511-9. https://doi.org/10.1093/cvr/cvt225
Wakui H, et al. Activation of Angiotensin II Type 1 Receptor-associated Protein Exerts an Inhibitory Effect On Vascular Hypertrophy and Oxidative Stress in Angiotensin II-mediated Hypertension. Cardiovasc Res. 2013 Dec 1;100(3):511-9. PubMed PMID: 24189624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension. AU - Wakui,Hiromichi, AU - Dejima,Toru, AU - Tamura,Kouichi, AU - Uneda,Kazushi, AU - Azuma,Koichi, AU - Maeda,Akinobu, AU - Ohsawa,Masato, AU - Kanaoka,Tomohiko, AU - Azushima,Kengo, AU - Kobayashi,Ryu, AU - Matsuda,Miyuki, AU - Yamashita,Akio, AU - Umemura,Satoshi, Y1 - 2013/11/04/ PY - 2013/11/6/entrez PY - 2013/11/6/pubmed PY - 2014/7/2/medline KW - Angiotensin receptor KW - Atherosclerosis KW - Hypertrophy KW - Oxidative stress KW - Vascular smooth muscle cells SP - 511 EP - 9 JF - Cardiovascular research JO - Cardiovasc. Res. VL - 100 IS - 3 N2 - AIMS: Activation of tissue angiotensin II (Ang II) type 1 receptor (AT1R) plays an important role in the development of vascular remodelling. We have shown that the AT1R-associated protein (ATRAP/Agtrap), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent pathological activation of the tissue renin-angiotensin system. In this study, we investigated the effects of ATRAP on Ang II-induced vascular remodelling. METHODS AND RESULTS: Transgenic (Tg) mice with a pattern of aortic vascular-dominant overexpression of ATRAP were obtained, and Ang II or vehicle was continuously infused into Tg and wild-type (Wt) mice via an osmotic minipump for 14 days. Although blood pressure of Ang II-infused Tg mice was comparable with that of Ang II-infused Wt mice, the Ang II-mediated development of aortic vascular hypertrophy was partially inhibited in Tg mice compared with Wt mice. In addition, Ang II-mediated up-regulation of vascular Nox4 and p22(phox), NADPH oxidase components, and 4-HNE, a marker of reactive oxygen species (ROS) generation, was significantly suppressed in Tg mice, with a concomitant inhibition of activation of aortic vascular p38MAPK and JNK by Ang II. This protection afforded by vascular ATRAP against Ang II-induced activation of NADPH oxidase is supported by in vitro experimental data using adenoviral transfer of recombinant ATRAP. CONCLUSION: These results indicate that activation of aortic vascular ATRAP partially inhibits the Nox4/p22(phox)-ROS-p38MAPK/JNK pathway and pathological aortic hypertrophy provoked by Ang II-mediated hypertension, thereby suggesting ATRAP as a novel receptor-binding modulator of vascular pathophysiology. SN - 1755-3245 UR - https://www.unboundmedicine.com/medline/citation/24189624/Activation_of_angiotensin_II_type_1_receptor_associated_protein_exerts_an_inhibitory_effect_on_vascular_hypertrophy_and_oxidative_stress_in_angiotensin_II_mediated_hypertension_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvt225 DB - PRIME DP - Unbound Medicine ER -