Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor
Angiotensin 1-7 (Ang 1-7) counter-regulates the cardiovascular actions of angiotensin II (Ang II). The present study investigated the protective effect of Ang 1-7 against Ang II-induced endoplasmic reticulum (ER) stress and endothelial dysfunction. Ex vivo treatment with Ang II (0.5 mu M, 24 hours)...
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my.um.eprints.160802019-12-16T09:28:23Z http://eprints.um.edu.my/16080/ Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor Murugan, Dharmani Devi Lau, Yeh Siang Lau, Wai Chi Mustafa, Mohd Rais Huang, Yu Q Science (General) T Technology (General) Angiotensin 1-7 (Ang 1-7) counter-regulates the cardiovascular actions of angiotensin II (Ang II). The present study investigated the protective effect of Ang 1-7 against Ang II-induced endoplasmic reticulum (ER) stress and endothelial dysfunction. Ex vivo treatment with Ang II (0.5 mu M, 24 hours) impaired endothelium-dependent relaxation in mouse aortas; this harmful effect of Ang II was reversed by co-treatment with ER stress inhibitors, l4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) as well as Ang 1-7. The Mas receptor antagonist, A779, antagonized the effect of Ang 1-7. The elevated mRNA expression of CHOP, Grp78 and ATF4 or protein expression of p-eIF2 alpha and ATF6 (ER stress markers) in Ang II-treated human umbilical vein endothelial cells (HUVECs) and mouse aortas were blunted by co-treatment with Ang 1-7 and the latter effect was reversed by A779. Furthermore, Ang II-induced reduction in both eNOS phosphorylation and NO production was inhibited by Ang 1-7. In addition, Ang 1-7 decreased the levels of ER stress markers and augmented NO production in HUVECs treated with ER stress inducer, tunicamycin. The present study provides new evidence for functional antagonism between the two arms of the renin-angiotensin system in endothelial cells by demonstrating that Ang 1-7 ameliorates Ang II-stimulated ER stress to raise NO bioavailability, and subsequently preserves endothelial function. Public Library of Science 2015 Article PeerReviewed Murugan, Dharmani Devi and Lau, Yeh Siang and Lau, Wai Chi and Mustafa, Mohd Rais and Huang, Yu (2015) Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor. PLoS ONE, 10 (12). e0145413. ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0145413 doi:10.1371/journal.pone.0145413 |
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Q Science (General) T Technology (General) Murugan, Dharmani Devi Lau, Yeh Siang Lau, Wai Chi Mustafa, Mohd Rais Huang, Yu Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
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Angiotensin 1-7 (Ang 1-7) counter-regulates the cardiovascular actions of angiotensin II (Ang II). The present study investigated the protective effect of Ang 1-7 against Ang II-induced endoplasmic reticulum (ER) stress and endothelial dysfunction. Ex vivo treatment with Ang II (0.5 mu M, 24 hours) impaired endothelium-dependent relaxation in mouse aortas; this harmful effect of Ang II was reversed by co-treatment with ER stress inhibitors, l4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) as well as Ang 1-7. The Mas receptor antagonist, A779, antagonized the effect of Ang 1-7. The elevated mRNA expression of CHOP, Grp78 and ATF4 or protein expression of p-eIF2 alpha and ATF6 (ER stress markers) in Ang II-treated human umbilical vein endothelial cells (HUVECs) and mouse aortas were blunted by co-treatment with Ang 1-7 and the latter effect was reversed by A779. Furthermore, Ang II-induced reduction in both eNOS phosphorylation and NO production was inhibited by Ang 1-7. In addition, Ang 1-7 decreased the levels of ER stress markers and augmented NO production in HUVECs treated with ER stress inducer, tunicamycin. The present study provides new evidence for functional antagonism between the two arms of the renin-angiotensin system in endothelial cells by demonstrating that Ang 1-7 ameliorates Ang II-stimulated ER stress to raise NO bioavailability, and subsequently preserves endothelial function. |
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Article |
author |
Murugan, Dharmani Devi Lau, Yeh Siang Lau, Wai Chi Mustafa, Mohd Rais Huang, Yu |
author_facet |
Murugan, Dharmani Devi Lau, Yeh Siang Lau, Wai Chi Mustafa, Mohd Rais Huang, Yu |
author_sort |
Murugan, Dharmani Devi |
title |
Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
title_short |
Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
title_full |
Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
title_fullStr |
Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
title_full_unstemmed |
Angiotensin 1-7 protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor |
title_sort |
angiotensin 1-7 protects against angiotensin ii-induced endoplasmic reticulum stress and endothelial dysfunction via mas receptor |
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Public Library of Science |
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2015 |
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http://eprints.um.edu.my/16080/ https://doi.org/10.1371/journal.pone.0145413 |
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1654960669437460480 |
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13.18916 |