INTERACTIONS CONTROLLING VITAMIN K-DEPENDENT COAGULATION

控制维生素 K 依赖性凝血的相互作用

• 批准号: 7667046
• 负责人: DARREL W STAFFORD
• 金额: $ 43.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7667046
• 关键词: Affect; Animal Model; Binding; Biochemical; Biochemistry; Biological Models; Blood Clot; Blood Coagulation Factor VII; Blood coagulation; Cause of Death; Cells; Coagulation Process; Collagen Type IV; Country; Disease; Dose; Elements; Enzymes; Factor IX; Goals; Health; Hemorrhage; Hemostatic function; Hydroquinones; Individual; Instruction; Lead; Methods; Modeling; Molecular Biology; Mus; Myocardial Infarction; Proteins; Research; Role; Stroke; System; Therapeutic; Thrombosis; United States; Variant; Vitamin K; Vitamins; base; cofactor; hydroquinone; improved; in vivo; intravital microscopy; tissue culture; vitamin K epoxide reductase

The long-term goal of this research is to understand the controlling interactions among key enzymes in the blood coagulation system. It is hoped that information derived from these studies will help improve treatments for, not only individuals with bleeding disorders, but also for those affected by the broader health problem, thrombosis. To accomplish these goals the studies will include the following specific research aims: 1) identify any cofactors or other accessory proteins that collaborate with vitamin K epoxide reductase in producing vitamin K hydroquinone; 2) investigate the structural elements controlling factor IX interactions with collagen IV and its role in coagulation; and 3) characterize the mechanism by which pharmacologic doses of factor Vila restore hemostasis. These aims will be achieved by using multifaceted approaches ranging from basic biochemistry and molecular biology to animal models. Studies will employ molecular biology, tissue culture, and biochemical methods to investigate the interaction of vitamin K epoxide reductase with other cellular proteins. Similar molecular biology and tissue culture methods will be used to create coagulation factor IX and factor VII variants which will be evaluated in a variety of model systems including a cell-based coagulation model and animal models including factor IX deficient mice and mice with factor IX that does not bind collagen IV. In vivo effects of these molecules will be evaluated by intravital microscopy.

这项研究的长期目标是了解血液凝固系统中关键酶之间的控制相互作用。希望从这些研究中获得的信息不仅有助于改善出血性疾病患者的治疗，而且有助于改善受血栓形成这一更广泛健康问题影响的患者的治疗。