Is Hyperglycemia the Culprit in Diabetes-accelerated Atherosclerosis?

• Applicant: Dr. Florian Willecke
• Subject Area: Cardiology, Angiology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218544770

Diabetes mellitus is associated with a number of cardiovascular complications. Most notably it is characterized by an increase in atherosclerosis. The reason for this is unclear and might affect the objectives of therapy to prevent or mitigate this complication in patients with both, type 1 and type 2 diabetes. A recent study showed that diabetes leads to a defect in regression of atherosclerosis and suggested that this may be due to hyperglycemia-mediated alterations of inflammatory cells contributing to atherosclerosis.I propose two aims to explore the relationship between hyperglycemia, inflammatory cells, and atherosclerosis: First, I will determine whether murine models of type 2 diabetes are associated with hyperglycemia-mediated alterations in white blood cells and whether pharmacologically and genetically induced glucose reduction will influence the phenotype of white blood cells. As murine models of type 2 diabetes I will use diet-induced obesity mice, leptin-deficient ob/ob mice, and GIRKO mice. Secondly, I will determine whether pharmacological glucose reduction alters the leukocyte phenotype in diabetes-associated atherosclerosis. As hyperlipidemia confounds the contribution of hyperglycemia in the commonly used atherosclerosis mouse models I will study the effect of glucose on atherosclerosis regression in diabetic mouse models after reducing plasma lipid levels.The interrogation of the hypothesis that glucose is the culprit in diabetes-accelerated atherosclerosis will likely result in the identification of novel targets at the interface of metabolic and cardiovascular disease. Given the dramatic epidemiology of both entities such novel therapeutic strategies are urgently needed and of general interest to attenuate the excessively high cardiovascular risk in patients with diabetes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ira Goldberg