Murine models to investigate the influence of diabetic metabolism on the development of atherosclerosis and restenosis.
Atherosclerosis and related forms of cardiovascular disease (CVD) are associated with several genetic and environmental risk factors, including hypercholesterolemia, diabetes mellitus (DM), hypertension, obesity and smoking. Human DM is a multi-system disorder that results from progressive failure of insulin production and insulin resistance. Most diabetic patients die from complications of atherosclerosis and CVD, and DM is also associated with increased risk of restenosis post-angioplasty. Furthermore, the incidence of DM, particularly type 2-DM, is expected to increase significantly during the next decades owing to the unhealthy effects of modern life-style habits (e.g., obesity and lack of physical exercise). Thus, it is of utmost importance to develop novel preventive and therapeutic strategies to reduce the social and health-care burden of CVD and DM. Although a number of physiological alterations thought to promote atherosclerosis have been identified in diabetic patients, the precise molecular mechanisms that link DM and atherosclerosis are largely unknown. Thus, the aim of this review is to discuss current murine models of combined DM and atherosclerosis and to explore how these experimental systems are being utilized to gain mechanistic insights into diabetes-induced neointimal lesion development, as well as their potential use in evaluating the efficacy of new therapies. Our discussion includes models generated by streptozotocin treatment and those resulting from naturally occurring or targeted mutations in the mouse.
Gonzalez-Navarro
Herminia
H
Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, Spain.
Burks
Deborah J
DJ
Andres
Vicente
V
D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003251:Constriction, Pathologic / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D051379:Mice; D012008:Recurrence; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D007328:Insulin; D020738:Leptin; D005947:Glucose