Cardiovascular disease remains the leading cause of death in the United States and vascular calcification and diabetes are both independent risk factors for incident cardiovascular disease. Fetuin-A is a hepatic secretory protein found in high concentrations in human serum and our preliminary studies suggest that feutin- A may simultaneously inhibit vascular calcification and promote insulin resistance and diabetes. We propose to explore the relationship of fetuin-A with the longitudinal development and progression of vascular calcification and diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The research evaluates biological mechanisms interlinked by a single protein and will provide new insights to cardiovascular biology and diabetology simultaneously. Conducting this research within MESA has a number of advantages. MESA stored sera from the baseline visit, allowing fetuin-A measurement. MESA extensively measured subclinical cardiovascular disease;therefore, all participants already have measurements of vascular calcification, vascular function, and metabolic parameters. Additionally, MESA participants were followed longitudinally, allowing for evaluation of the associations of baseline fetuin-A concentrations with incident vascular calcification and diabetes. We propose to take advantage of this rich resource to explore the following primary aims: (1) To determine the cross-sectional and longitudinal associations of fetuin-A with vascular calcification and vascular function;and (2) To determine the associations of serum fetuin-A concentrations with adiposity, impaired fasting glucose, and diabetes mellitus. This research will take advantage of the hypothesized countervailing effects of fetuin-A on vascular calcification and diabetes to provide new insights to cardiovascular disease pathogenesis.
While cardiovascular disease and diabetes represent common and morbid diseases, our understanding of their pathogenesis remains incomplete. The results of this epidemiologic study will provide novel insights into their pathogenesis and may ultimately identify novel therapeutic targets for their prevention or treatment.
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