MATRIX GLA PROTEIN AND ARTERY CALCIFICATION

描述(改编自调查人员摘要)：本报告的目标 调查是为了确定华法林治疗的贡献和 膳食维生素K缺乏对人体动脉钙化过程的影响 在这种疾病的大鼠模型中。首席调查员将评估 基质GLA蛋白，即维生素K的分子机制 依赖，可抑制动脉钙化过程。申请人 将确定那些与华法林协同作用的风险因素 在大鼠模型中加速动脉钙化。他将建立 动脉钙化停止或逆转的程度。在 在这一特定目标的背景下，他将调查饮食的影响 GLA蛋白羧化缺陷与钙化 大鼠的动脉。普赖斯博士还将确定华法林的效果 动脉粥样硬化动物模型中内膜钙化的研究 探讨GLA蛋白进入动脉的能力 由华法林引起的钙化。第二个目标，旨在 血清GLA羧化缺陷与发病关系的探讨 蛋白质与动脉钙化的等电聚焦和末端检测 蛋白质测序；将进行矿物质结合活性测量 羧化状态。他还将研究其结构和功能 人类动脉中Gla蛋白与钙化部位的关系。 首席调查员还将调查 GLA蛋白抑制人主动脉中膜弹性蛋白的钙化 将弹性蛋白添加到含有生理浓度的溶液中 钙和磷酸盐。他还将确定GLA蛋白的作用是 一种抑制人主动脉分离晶体生长的药物 媒体。进行这些实验是为了确定 维生素K缺乏和华法林治疗是高血压的危险因素 人体动脉的钙化。

DESCRIPTION (Adapted from Investigator's Abstract): The objectives of this investigation are to define the contribution of warfarin treatment and of dietary vitamin K deficiency to the arterial calcification process in humans and in a rat model of the disease. The Principal Investigator will assess the molecular mechanism by which matrix Gla proteins, which are vitamin K dependent, can inhibit the arterial calcification process. The applicant will identify those risk factors which act synergistically with warfarin to accelerate arterial calcification in a rat model. He will establish the extent to which arterial calcification is arrested or reversed. Within the context of this specific aim, he will investigate the effect of dietary deficiency on the carboxylation of the Gla protein and the calcification in arteries in the rat. Dr. Price will also determine the effect of warfarin on the calcification of the intima in animal models of atherosclerosis and investigate the ability of the Gla protein infusion the arterial calcification that is induced by warfarin. The second aim, is designed to investigate the relationship between defective carboxylation of serum Gla protein and arterial calcification using isoelectric focusing and terminal protein sequencing; mineral binding activity will be done to measure carboxylation status. He will also look at the structure and functional associations of Gla protein and calcification sites in the human artery. The principal investigator will also investigate the mechanism by which the Gla proteins inhibit the calcification of elastin in the human aortic media when elastin is added to solutions that contain physiological concentrations of calcium and phosphate. He will also determine the role of Gla protein as an inhibitor of the growth of crystallites isolated by the human aortic media. These experiments are being done to establish the importance of vitamin K deficiency and of warfarin treatment as risk factors for the calcification of human arteries.