New and rapid diagnostic method for cardiovascular disease and prothrombotic state

心血管疾病和血栓前状态的新型快速诊断方法

• 批准号: 06557063
• 负责人: MIYATA Toshiyuki
• 金额: $ 4.54万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06557063/
• 关键词: coagulation factor VII; cardiovascular disease; diabetics; stroke; coronary artery disease; prethrombotic state; thrombosis; diagnosis; 臨床検査法; 凝固亢進状態; 第VII因子

Factor VII (FVII) plays an important role in initiation of the tissue factor-induced coagulation pathway and an increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. However, it remains uncertain whether high FVIIc levels are due to an increase in the activation of FVII or due to an increase in the concentration of FVII mass. We developed a new fluorogenic assay for plasma activated FVII (FVIIa) using soluble tissue factor. The sensitivity of this assay ranged from 0.2 to 1,000 ng of FVIIa per milliliter of plasma. Plasma FVIIa levels were measured in 110 healthy subjects and 93 patients with hypertension, diabetes mellitus, and/or cardiovascular disease. The mean plasma FVIIa level in healthy Japanese individuals was 2.5 ng/ml and it was lower than that in Western subjects. Aging increased both the FVIIa level and FVII mass, while menopause mainly increased the FVII mass. Elderly patients with coronary artery disease and/or chronic cerebral infarction showed an increase in the plasma FVIIa levels and the FVIIa/FVIIag ratio. Arterial cardiovascular disease was more common in a high-FVIIa elderly group than in a low-FVIIa elderly group. Plasma FVIIa levels were not correlated with the serum levels of total cholesterol or triglycerides. The FVIIa level and the FVIIa/FVIIag ratio were positively correlated with the fibrinogen level and were negatively correlated with the body mass index and the serum albumin level in the elderly. In conclusion, aging, cardiovascular disease, and malnutrition increased the plasma FVIIa level. FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.

凝血因子VII(FVII)在启动组织因子诱导的凝血途径中起着重要作用，凝血因子活性升高(FVIIc)已被认为是冠状动脉疾病的独立危险因素。然而，目前尚不确定FVIIc水平高是由于Fvii激活增加还是由于Fvii质量浓度增加。我们用可溶性组织因子建立了一种新的血浆活化FVII(FVIIa)的荧光分析方法。该检测方法的灵敏度为每毫升血浆0.2至1,000 ng FVIIa。测定了110例健康人和93例高血压、糖尿病和/或心血管疾病患者的血浆FVIIa水平。健康日本人血浆FVIIa平均水平为2.5 ng/ml，低于西方人群。增龄使FVIIa水平和FVII质量均增加，绝经后FVIIa和FVII质量主要增加。老年冠心病和(或)慢性脑梗塞患者血浆FVIIa水平及FVIIa/FVIIag比值升高。动脉心血管疾病在高FVIIa老年组比低FVIIa老年组更常见。血浆FVIIa水平与血清总胆固醇或甘油三酯水平无相关性。老年人FVIIa水平、FVIIa/FVIIag比值与纤维蛋白原水平呈正相关，与体重指数、血清白蛋白水平呈负相关。总而言之，衰老、心血管疾病和营养不良增加了血浆FVIIa水平。FVIIa水平与血脂水平及肝脏合成活性无相关性，提示FVIIa可能是心血管疾病的独立危险因素。

项目成果

K.Kario, T,Matsuo, H.Kobayashi, T.Sakata, T.Miyata, K.Shimada: "Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged *75 years." Atherosclerosis. 116. 211-219 (1995)

K.Kario、T、Matsuo、H.Kobayashi、T.Sakata、T.Miyata、K.Shimada：“75 岁日本健康老年人中与空腹胰岛素水平相关的止血紊乱的性别差异。”

T.Miyata ら: "Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency." Thromb,Haemost. 71. 32-37 (1994)

T. Miyata 等人：“C 蛋白重链中的三个错义突变导致 I 型和 II 型 C 蛋白缺陷。”Thromb，Haemost，71. 32-37 (1994)。

T.Miyata ら: "Factor IX Bm Kiryu:A Val-313-to-Asp substitution in the catalytic domain results in loss of function due to a conformational change of…" Br.I.Haematal,. 88. 156-165 (1994)

T.Miyata 等人：“因子 IX Bm Kiryu：催化结构域中的 Val-313-Asp 取代导致由于构象变化而导致功能丧失……”Br.I.Haematal，88. 156- 165 (1994)

Y.Z.Zheng ら: "Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modeling." Blood Coagul,Fibrinolysis. 5. 687-696 (1994)

Y.Z.Zheng 等人：“与 I 型和 II 型蛋白 C 缺乏相关的六种错义突变以及从分子模型获得的影响。” 5. 687-696 (1994)

宮田敏行: "「ビタミンK(医学・生物学領域における新展開)」V.ビタミンK依存性蛋白質の構造とその機能、A.プロトロンファミリー、2)VII因子" メディカル ジャーナル社, 18 (1994)

Toshiyuki Miyata：“维生素 K（医学和生物领域的新发展）”V. 维生素 K 依赖性蛋白质的结构和功能，A. Protron 家族，2) ​​因子 VII，Medical Journal Inc.，18 (1994)