title: Cardiovascular inflammation is reduced with methotrexate in diabetes.
abstract: Diabetes increases the risk of vascular events and mortality. While earlier type 2 diabetes trials demonstrated that intensive glucose lowering reduces microvascular complications, it is only recently that treatment with some of the newer antihyperglycemic agents has been associated with macrovascular benefits. We report herein that db/db mice concomitantly fed the Western diet and treated with the anti-inflammatory agent methotrexate display a less aggressive inflammatory (lower serum IL-1β, IL-6, SDF-1, and TNFα levels; higher circulating adiponectin, IL-12p70 and IL-10 concentrations; lower aortic VCAM-1 levels) profile than their saline-treated counterpart. Furthermore, acetylcholine-elicited endothelium-dependent vasodilatation was significantly greater in thoracic aortic segments from the former group. Collectively, the data lend support to the notion that alterations in the inflammatory system may be involved in the macrovascular benefits observed in type 2 diabetes trials and provide credence for the development of anti-inflammatory tools to lower CV risk and CV events in diabetes.
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Quan
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.|Division of Vascular Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Department of Surgery, University of Toronto, Toronto, Canada.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Polemidiotis
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.|Division of Endocrinology & Metabolism, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.
authors.forename: Hwee
authors.initials: H
authors.lastname: Teoh
authors.affiliation: Division of Cardiology, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.affiliation: Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 8th Floor Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca.|Department of Surgery, University of Toronto, Toronto, Canada. vermasu@smh.ca.
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D008727:Methotrexate
keywords: Diabetes; Inflammation; Methotrexate