Cardiovascular Metabolism and Complications
Group leaders are Drs. Daniel Rader, Michael Parmacek, Frederick SamahaThis Scientific focus of the DERC is linked to the IDOM Cardiovascular Metabolism Unit.
The mission of the Penn DERC 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 DERC. Penn DERC investigators also have expertise in neurological, ophthamological, and renal complications of diabetes.
Highlights of Significant Findings
Over the past five years, Penn DERC investigators have become particularly interested in metabolic syndrome/insulin resistance syndrome and its role in atherosclerotic risk. Dr. Rader's group elegantly demonstrated that inhibition of endothelial lipase, which his group has championed as a major regulator of lipid metabolism increases serum HDL levels. Dr. Rader's basic interest in HDL was complemented by an exciting finding that pharmacological inhibition of cholesterol ester transfer protein markedly increased HDL cholesterol levels and lowered LDL cholesterol levels in patients with low HDL levels.
Dr. Parmacek's group performed important studies that have highlighted the role of myocardin as a transcriptional regulator of the differentiation of smooth muscle cells, whose proliferation is a key element of atherosclerosis. Another important complication of diabetes is ophthalmopathy leading to blindness, and Dr. Bennett's pioneering work in gene therapy has been highly promising in preclinical trials.
Dr. Lazar's group found that hepatic LXR controls lipid metabolism in a diet-dependent manner that impacts atherosclerosis. Dr. Fitzgerald reported that COX2 has atheroprotective-effects that may underly the cardiovascular risk of pharmaceutical inhibitors such as Vioxx. An additional, debilitating complication of diabetes is peripheral neuropathy, and Dr. Scherer made great progress in understanding neuropathic mechanisms. Dr. Reilly, a new investigator funded by a DERC pilot and feasibility grant made great progress in patient oriented investigation of links between type 2 diabetes and atherosclerosis, including the first demonstration of increased resistin levels in humans with atherosclerosis, which has now been confirmed by several other groups.