Cardiovascular Metabolism and Complications
Group leaders are Drs. Daniel Rader, Muredach Reilly, and Michael Parmacek
This Scientific focus of the DRC is linked to the IDOM Cardiovascular Metabolism Unit.
The mission of the Penn DRC includes understanding, preventing, and treating the complications of diabetes. Atherosclerotic cardiovascular disease, which is the leading cause of death of diabetics and patients with insulin resistance, is a particular emphasis of the DRC. Penn DRC investigators also have expertise in neurological, ophthamological, and renal complications of diabetes.
Highlights From 2006-Present:
Penn DRC investigators explore many aspects of diabetic complications, and have become particularly interested in metabolic syndrome/insulin resistance syndrome and its role in cardiovascular disease. The Transgenic and Chimeric Mouse, Mouse Phenotyping, Physiology, and Metabolism, RIA/Biomarker, and Viral Vector Cores have been essential for the success of this Focus Area. Three research highlight areas during the past period are noted below, all translational or potentially translational to humans.
Highlight one: Control of serum cholesterol levels in humans. Dr. Rader's group elegantly demonstrated that loss of function mutations in endothelial lipase increase serum HDL cholesterol in humans (Edmondson JCI 2009), while elegantly providing the mechanism by which LDL cholesterol levels are regulated by a SNP that alteres expression of the sortilin gene (Musunuru Nature 2010).
Highlight two: Role of phospholipase A2 in diabetes-associated atherosclerosis. Dr. Wilensky has developed a diabetic pig model that, unlike murine models, develops atherosclerosis in a manner similar to human diabetics. Using this model in collaboration with Dr. Mohler, he demonstrated that pharmacological inhibition of phospholipase A2 reduced coronary atherosclerosis, suggesting a potential new therapy for macrovascular disease in diabetics (Wilensky Nature Medicine 2008).
Highlight three: Translational research in microvascular diabetic complications. Diabetic ophthalmopathy is the leading cause of blindness, and Dr. Bennett's pioneering work in ocular gene therapy has led to exciting new treatments for a rare condition (Leber's congenital amaurosis) that represent proof-of-concept for ocular gene therapy in more common diabetic eye disease (Maquire NEJM 2008; Maguire, Lancet 2009). In addition, Drs. Feldman led an NIDDK-sponsored study demonstrating that dipyridamole plus aspirin reducing the risk of stenosis in hemodialysis grafts in a patient population with a large number of diabetics (Dixon NEJM 2009).