Role of gamma' Fibrinogen in Cardiovascular Disease

γ纤维蛋白原在心血管疾病中的作用

• 批准号: 7012824
• 负责人: DAVID Henry FARRELL
• 金额: $ 14.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012824
• 关键词: acute phase protein; biomarker; blood lipoprotein; cardiovascular disorder risk; clinical research; diabetes mellitus; fibrinogen; human data; human tissue; hypertension; inflammation; protein isoforms; tobacco abuse

DESCRIPTION (provided by applicant): Elevated levels of plasma fibrinogen, the major structural protein of blood clots, are strongly associated with cardiovascular disease. But while fibrinogen fulfills many etiological criteria, it remains unclear whether elevated levels of fibrinogen are an important cause of cardiovascular disease or an effect of it. This link between fibrinogen and cardiovascular disease may lie not only in the level of plasma fibrinogen, but also in its composition. We found that elevated levels of a minor fibrinogen isoform called gamma prime (gammaA/gamma') fibrinogen were associated with coronary artery disease. This observation is consistent with findings from an independent research group, who reported an association between the ratio of gammaA/gamma' fibrinogen to total fibrinogen and arterial thrombosis. To date, however, no study has directly tested the association between gammaA/gamma' fibrinogen and traditional cardiovascular disease risk factors (e.g. smoking, hypertension, diabetes, and cholesterol). Furthermore, the clinical and biochemical properties of gammaA/gamma' fibrinogen implicate it in direct mediation of cardiovascular disease pathogenesis. In this application, we propose three Specific Aims: 1) To determine the distribution of gammaA/gammaA fibrinogen and gammaAgamma' fibrinogen among the Framingham Offspring cohort and investigate gender- and age-specific characteristics. 2) To determine the relationship between fibrinogen isoforms and established cardiovascular disease risk factors. 3) To determine if the fibrinogen isoforms in plasma are independently associated with CVD.

描述（由申请人提供）：血浆纤维蛋白原（血栓的主要结构蛋白）水平升高与心血管疾病密切相关。尽管纤维蛋白原满足许多病因学标准，但仍不清楚纤维蛋白原水平升高是否是心血管疾病的重要原因或其影响。纤维蛋白原与心血管疾病之间的这种联系可能不仅在于血浆纤维蛋白原的水平，还在于其成分。我们发现，一种称为γ'（gammaA/gamma'）纤维蛋白原的次要纤维蛋白原亚型水平升高与冠状动脉疾病相关。这一观察结果与一个独立研究小组的发现一致，该研究小组报告了γA/γ'纤维蛋白原与总纤维蛋白原的比率与动脉血栓形成之间的关联。然而，迄今为止，还没有研究直接测试γA/γ'纤维蛋白原与传统心血管疾病危险因素（例如吸烟、高血压、糖尿病和胆固醇）之间的关联。此外，γA/γ'纤维蛋白原的临床和生化特性表明它直接介导心血管疾病的发病机制。在此应用中，我们提出了三个具体目标： 1) 确定 Framingham 后代队列中 gammaA/gammaA 纤维蛋白原和 gammaAgamma' 纤维蛋白原的分布，并研究性别和年龄特异性特征。 2) 确定纤维蛋白原亚型与已确定的心血管疾病危险因素之间的关系。 3) 确定血浆中的纤维蛋白原亚型是否与CVD独立相关。

项目成果

Severe bleeding in a woman heterozygous for the fibrinogen gammaR275C mutation.

• DOI: 10.1097/mbc.0b013e3283393c7c
• 发表时间: 2010-07
• 期刊: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
• 作者: Rein CM;Anderson BL;Ballard MM;Domes CM;Johnston JM;Madsen RJ Jr;Wolper KK;Terker AS;Strother JM;Deloughery TG;Farrell DH
• 通讯作者: Farrell DH