Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic
Annual rept. 1 Jan 2005-30 Nov 2006
COLUMBIA UNIV NEW YORK
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There is an epidemic of obesity in the military. Obesity leads to insulin resistance syndromes, notably metabolic syndrome and type 2 diabetes. The major cause of death in these syndromes is atherothrombotic vascular disease, including coronary artery disease. Therefore, when retired military personnel and their families reach middle age, there will be an epidemic of obesity-related vascular disease. The studies completed as part of this project have revealed new cellular and molecular links between obesityinsulin resistance and atherothrombotic vascular disease. We have shown that a side effect of a class of insulin-sensitizing PPAR yamma-activating drugs called TZDs, which are used widely in obese people, may promote vascular disease. We have also shown how adiponectin, a hormone that is decreased in obese subjects, might protect against vascular disease. These advances suggest new ideas for drug therapy a super TZD that would eliminate the potential pro-atherogenic effects and an adiponectin mimetic, which would protect macrophages from advanced lesional apoptosis. If successful, these drugs would help stem the rising tide of obesity-related heart disease in middle-aged and older military personnel and their families as well as in the general population.
- Anatomy and Physiology
- Medicine and Medical Research