Unfavorable metabolic conditions and diseases, including obesity, diabetes, and hyperlipidemia, are major causes for cardiovascular disease in the Western World and yet the early detection and monitoring of the adverse effects of metabolic disease on the heart and vasculature remain elusive. Inflammation, oxidative stress, enhanced accumulatin of lipids, and lipid peroxidation in the heart and vasculature are at the root of diastolic heart failure, hypertension, and cardiac and vascular hypertrophy, stiffening, and dysfunction. Somwhat stereotypical, nonspecific changes do occur in plasma protein indicators of inflammation and oxidants as evidence of systemic metabolic disease. The underlying hypothesis of this project is that the specificity of detecting cardiovascular disease of metabolic causes will be greatly increased by a targeted proteomic approach to detect teh effects of abnormal metabolism on proteins. The project will take advantage of discoveries that multiple covalent oxidative and reactive lipid and glycation modifications occur on plasma proteins in patients with pulmonary hypertension or with systemic amyloid disease. The goal here is to examine which proteins within the diseased heart and vasculature are modified and what modifications occur in response to metabolic disease, and then to identify a subset of these modified proteins that show potential for use as tissue specific biomarkers of the disease.
