Fetuin-A: A Novel Biomarker of Vascular Calcification and Diabetes Mellitus

描述（由申请人提供）：心血管疾病仍然是美国的主要死亡原因，血管钙化和糖尿病都是心血管疾病事件的独立风险因素。胎球蛋白-A是一种在人血清中高浓度存在的肝脏分泌蛋白，我们的初步研究表明，胎球蛋白- A可能同时抑制血管钙化和促进胰岛素抵抗和糖尿病。我们建议在多种族动脉粥样硬化研究（梅萨）队列中探讨胎球蛋白A与血管钙化和糖尿病纵向发展和进展的关系。该研究评估了由单一蛋白质相互联系的生物学机制，并将同时为心血管生物学和糖尿病学提供新的见解。在梅萨内进行这项研究有许多优点。梅萨储存来自基线访视的血清，允许胎球蛋白-A测量。梅萨广泛测量亚临床心血管疾病;因此，所有参与者都已经测量了血管钙化，血管功能和代谢参数。此外，对梅萨参与者进行纵向随访，以评估基线胎球蛋白A浓度与血管钙化和糖尿病的关系。我们建议利用这一丰富的资源，探索以下主要目标：（1）确定胎球蛋白-A与血管钙化和血管功能的横截面和纵向关联;（2）确定血清胎球蛋白-A浓度与肥胖、空腹血糖受损和糖尿病的关联。这项研究将利用胎球蛋白-A对血管钙化和糖尿病的假设抵消作用，为心血管疾病的发病机制提供新的见解。公共卫生相关性：虽然心血管疾病和糖尿病是常见的病态疾病，但我们对其发病机制的理解仍然不完整。这项流行病学研究的结果将为他们的发病机制提供新的见解，并可能最终确定新的治疗目标，以预防或治疗。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.