{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:45:09Z","timestamp":1774327509249,"version":"3.50.1"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T00:00:00Z","timestamp":1353888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CCT 83030"],"award-info":[{"award-number":["CCT 83030"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 97912"],"award-info":[{"award-number":["MOP 97912"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000241","name":"Physicians' Services Incorporated Foundation","doi-asserted-by":"publisher","award":["PSI 09-42"],"award-info":[{"award-number":["PSI 09-42"]}],"id":[{"id":"10.13039\/501100000241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Impaired endothelial repair is a key contributor to microvascular rarefaction and consequent end-organ dysfunction in diabetes. Recent studies suggest an important role for bone marrow-derived early outgrowth cells (EOCs) in mediating endothelial repair, but the function of these cells is impaired in diabetes, as in advanced age. We sought to determine whether diabetes-associated EOC dysfunction might be attenuated by pharmacological activation of silent information regulator protein 1 (SIRT1), a lysine deacetylase implicated in nutrient-dependent life span extension in mammals. Despite being cultured in normal (5.5 mM) glucose for 7 days, EOCs from diabetic rats expressed less SIRT1 mRNA, induced less endothelial tube formation in vitro and neovascularization in vivo, and secreted less of the proangiogenic ELR+ CXC chemokines CXCL1, CXCL3, and CXCL5. Ex vivo SIRT1 activation restored EOC chemokine secretion and increased the in vitro and in vivo angiogenic activity of EOC conditioned medium derived from diabetic animals to levels similar to that derived from control animals. These findings suggest a pivotal role for SIRT1 in diabetes-induced EOC dysfunction and that its pharmacologic activation may provide a new strategy for the restoration of EOC-mediated repair mechanisms.<\/jats:p>","DOI":"10.5966\/sctm.2012-0026","type":"journal-article","created":{"date-parts":[[2012,11,27]],"date-time":"2012-11-27T05:36:16Z","timestamp":1353994576000},"page":"921-926","source":"Crossref","is-referenced-by-count":18,"title":["Angiogenic Dysfunction in Bone Marrow-Derived Early Outgrowth Cells from Diabetic Animals Is Attenuated by SIRT1 Activation"],"prefix":"10.1093","volume":"1","author":[{"given":"Darren A.","family":"Yuen","sequence":"first","affiliation":[{"name":"Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Department of Medicine, Toronto, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Keenan Research Centre of the 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