MATRIX GLA PROTEIN AND ARTERY CALCIFICATION

基质 GLA 蛋白和动脉钙化

• 批准号: 6030808
• 负责人: PAUL ARMS PRICE
• 金额: $ 31.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030808
• 关键词: artery; atherosclerosis; calcification; carboxylation; clinical research; disease /disorder model; disease /disorder proneness /risk; drug interactions; elastin; human tissue; isoelectric point; laboratory rat; nutrient drug interaction; nutrition related tag; protein sequence; protein structure function; vitamin K deficiency; warfarin

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.

描述（改编自研究者摘要）：本研究的目的 研究的目的是确定华法林治疗和 膳食维生素K缺乏对人类动脉钙化过程的影响 以及该疾病的大鼠模型。 主要研究者将评估 基质Gla蛋白，即维生素K， 依赖，可以抑制动脉钙化过程。 申请人 将确定与华法林协同作用的风险因素， 加速大鼠模型中的动脉钙化。 他将建立 动脉钙化被阻止或逆转的程度。 内 在这个特定目标的背景下，他将研究饮食的影响， Gla蛋白羧化和钙化的缺陷， 老鼠的动脉 普莱斯博士还将确定华法林的效果 对动脉粥样硬化动物模型内膜钙化的影响， 探讨Gla蛋白经动脉灌注的能力 华法林引起的钙化。 第二个目标是， 探讨血清Gla羧化缺陷与糖尿病的关系 蛋白质和动脉钙化，使用等电聚焦和终端 蛋白质测序;将进行矿物质结合活性以测量 羧化状态 他还将研究结构和功能 Gla蛋白与人体动脉钙化部位的相关性。 主要研究者还将研究 GLA蛋白抑制人主动脉中膜弹性蛋白钙化 当将弹性蛋白加入到含有生理浓度的溶液中时 钙和磷酸盐。 他还将确定Gla蛋白的作用， 一种抑制人体主动脉分离的微晶生长的抑制剂 媒体 这些实验是为了证明 维生素K缺乏和华法林治疗是 人体动脉的钙化