Cardiovascular inflammation is reduced with methotrexate in diabetes.

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.