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The current study aimed to investigate whether miR-181b ameliorates diabetes-associated endothelial dysfunction, and to identify potential molecular mechanisms and upstream inducer of miR-181b. We found that miR-181b level was decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics improved endothelium-dependent vasodilation in aortas of high fat diet (HFD)\/streptozotocin (STZ)-induced diabetic mice, accompanied by suppression of superoxide overproduction and vascular inflammation markers. AMPK activator-induced AMPK activation upregulated miR-181b level in human umbilical vein endothelial cells (HUVECs). Chronic exercise, potentially through increased blood flow, activated AMPK\/miR-181b axis in aortas of diabetic mice. Exposure to laminar shear stress upregulated miR-181b expression in HUVECs. Overall, our findings highlight a critical role of AMPK\/miR-181b axis and extend the benefits of chronic exercise in counteracting diabetes-associated endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/antiox11061137","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Activation of AMPK\/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Chak-Kwong","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China"},{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-7997","authenticated-orcid":false,"given":"Wai-San","family":"Cheang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Zhuhai 519000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Wai","family":"Lau","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9087-227X","authenticated-orcid":false,"given":"Jiang-Yun","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-9646","authenticated-orcid":false,"given":"Chi-Fai","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China"},{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China"},{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12933-020-01159-5","article-title":"Global Trend of Diabetes Mortality Attributed to Vascular Complications, 2000\u20132016","volume":"19","author":"Ling","year":"2020","journal-title":"Cardiovasc. 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