{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:35:46Z","timestamp":1792690546937,"version":"4.5.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Angiotensin-converting enzyme 2 (ACE2)\u2013angiotensin (1-7) [Ang (1-7)]-Mas constitutes the vasoprotective axis and is demonstrated to antagonize the vascular pathophysiological effects of the classical renin\u2013angiotensin system. We sought to study the hypothesis that upregulation of ACE2-Ang (1-7) signaling protects endothelial function through reducing oxidative stress that would result in beneficial outcome in diabetes.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:italic toggle=\"yes\">Ex vivo<\/jats:italic>\n                    treatment with Ang (1-7) enhanced endothelium-dependent relaxation (EDR) in renal arteries from diabetic patients. Both Ang (1-7) infusion\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    osmotic pump (500\u2009ng\/kg\/min) for 2 weeks and exogenous ACE2 overexpression mediated by adenoviral ACE2\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    tail vein injection (10\n                    <jats:sup>9<\/jats:sup>\n                    pfu\/mouse) rescued the impaired EDR and flow-mediated dilatation (FMD) in\n                    <jats:italic toggle=\"yes\">db\/db<\/jats:italic>\n                    mice. Diminazene aceturate treatment (15\u2009mg\/kg\/day) activated ACE2, increased the circulating Ang (1-7) level, and augmented EDR and FMD in\n                    <jats:italic toggle=\"yes\">db\/db<\/jats:italic>\n                    mouse arteries. In addition, activation of the ACE2-Ang (1-7) axis reduced reactive oxygen species (ROS) overproduction determined by dihydroethidium staining, CM-H\n                    <jats:sub>2<\/jats:sub>\n                    DCFDA fluorescence imaging, and chemiluminescence assay in\n                    <jats:italic toggle=\"yes\">db\/db<\/jats:italic>\n                    mouse aortas and also in high-glucose-treated endothelial cells. Pharmacological benefits of ACE2-Ang (1-7) upregulation on endothelial function were confirmed in ACE2 knockout (ACE2 KO) mice both\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    .\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    We elucidate that the ACE2-Ang (1-7)-Mas axis serves as an important signal pathway in endothelial cell protection in diabetic mice, especially in diabetic human arteries.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Endogenous ACE2-Ang (1-7) activation or ACE2 overexpression preserves endothelial function in diabetic mice through increasing nitric oxide bioavailability and inhibiting oxidative stress, suggesting the therapeutic potential of ACE2-Ang(1-7) axis activation against diabetic vasculopathy.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                    . 23, 880\u2013892.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6070","type":"journal-article","created":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T12:07:53Z","timestamp":1428926873000},"page":"880-892","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":71,"title":["Upregulation of Angiotensin (1-7)-Mediated Signaling Preserves Endothelial Function Through Reducing Oxidative Stress in Diabetes"],"prefix":"10.1177","volume":"23","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Yun","family":"Luo","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Yu","family":"Tian","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai San","family":"Cheang","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Wai","family":"Lau","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Tak","family":"Wong","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Houston Methodist Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Ming","family":"Wong","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Yao","family":"Lan","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Yao","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan K.","family":"Raizada","sequence":"additional","affiliation":[{"name":"University of Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese University of Hong Kong","place":["China"]},{"name":"Chinese University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,10,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000108758"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0782"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.3.523"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000175813.04375.8a"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.00202"},{"issue":"3","key":"e_1_3_3_7_2","first-page":"S54","article-title":"Endothelial dysfunction in diabetes mellitus","volume":"32","author":"Cosentino F","year":"1998","unstructured":"Cosentino F, and Luscher TF. 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