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Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)\u2010induced type 1 diabetic rats, FoxO1 expression was up\u2010regulated in carotid arteries at 8\u00a0weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross\u2010sectional area, media\u2010to\u2010lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg\/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro\u2010inflammatory factors, adhesion factors, apoptosis, NOD\u2010like receptor family protein\u20103 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down\u2010regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes\u2010induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes\u2010associated cardiovascular diseases.<\/jats:p>","DOI":"10.1111\/jcmm.15935","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T19:40:12Z","timestamp":1603827612000},"page":"13727-13738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Up\u2010regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats"],"prefix":"10.1111","volume":"24","author":[{"given":"Jingjin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of 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