title: Uncomplicating the Macrovascular Complications of Diabetes: The 2014 Edwin Bierman Award Lecture.
abstract: The risk of cardiovascular events in humans increases in the presence of type 1 or type 2 diabetes mellitus, in large part due to exacerbated atherosclerosis. Genetically engineered mouse models have begun to elucidate cellular and molecular mechanisms responsible for diabetes-exacerbated atherosclerosis. Research on these mouse models has revealed that diabetes independently accelerates initiation and progression of lesions of atherosclerosis and also impairs the regression of lesions following aggressive lipid lowering. Myeloid cell activation in combination with proatherogenic changes allowing for increased monocyte recruitment into arteries of diabetic mice has emerged as an important mediator of the effects of diabetes on the three stages of atherosclerosis. The effects of diabetes on atherosclerosis appear to be dependent on an interplay between glucose and lipids, as well as other factors, and result in increased recruitment of monocytes into both progressing and regressing lesions of atherosclerosis. Importantly, some of the mechanisms revealed by mouse models are now being studied in human subjects. This Perspective highlights new mechanistic findings based on mouse models of diabetes-exacerbated atherosclerosis and discusses the relevance to humans and areas in which more research is urgently needed in order to lessen the burden of macrovascular complications of type 1 and type 2 diabetes mellitus.
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology and Nutrition and Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA bornf@u.washington.edu.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
mesh_terms: D000818:Animals; D001363:Awards and Prizes; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice