Mouse models for studies of cardiovascular complications of type 1 diabetes

Mouse models represent a powerful tool for investigating the underlying mechanisms of disease. Type 1 diabetes results in a markedly increased risk of cardiovascular disease. The cardiovascular complications are manifested primarily as ischemic heart disease caused by accelerated atherosclerosis, but also as cardiomyopathy, defined as ventricular dysfunction in the absence of clear ischemic heart disease. Several mouse models are now available to study atherosclerosis and cardiomyopathy associated with type 1 diabetes. For studies of diabetes-accelerated atherosclerosis, these models include low-density lipoprotein (LDL) receptor-deficient and apolipoprotein E-deficient mice in which diabetes is induced by streptozotocin or viral infection. In these mouse models, type 1 diabetes can be induced without marked changes in plasma lipid levels, thereby mimicking the accelerated atherosclerosis seen in patients with type 1 diabetes. However, mouse models that exhibit thrombotic events and myocardial infarctions as a result of diabetes still need to be developed. Conversely, cardiomyopathy associated with diabetes has now been extensively evaluated in streptozotocin-treated C57BL/6 mice, and in transgenic mice expressing calmodulin under a beta-cell-specific promoter. These mouse models have given significant insight into the molecular mechanisms causing cardiomyopathy, and indicate that increased oxidative stress contributes to diabetes-associated cardiomyopathy. In this review, we will discuss the available mouse models for studies of cardiovascular complications of type 1 diabetes, the potential mechanisms underlying these complications, and the need for new and improved mouse models.