A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction.
A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction.
复制标题
DOI：
10.3389/fcvm.2022.919394
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Goodall, Alison H.
中科院分区：
文献类型：
--
作者：
Dunster, Joanne L.;Wright, Joy R.;Samani, Nilesh J.;Goodall, Alison H.
提高对决定止血反应程度的关键因素的理解，可能有助于识别因动脉粥样硬化血栓形成事件（如急性心肌梗死（MI））而有产生闭塞性血栓风险的个体。虽然纤维蛋白原水平是MI的公认危险因素，但血栓形成风险与其他凝血蛋白的相关性并不一致。这可能是由于任何个体中的促凝血因子和抗凝因子的复杂平衡。我们比较了162名早期心肌梗死患者（MI <50岁）和186名年龄和性别匹配的无CAD病史的健康对照者血浆中前抗凝蛋白和抗凝蛋白的测定水平。然后，我们使用这些个体的测量值作为已建立数学模型的输入，以研究止血因素的微小变化如何影响止血反应的总体幅度，并确定男性和女性患者和对照组止血反应的差异关键驱动因素。与对照组相比，MI患者血浆中组织因子（P = 0.007）、tenase组分（FIX和FVIII; P < 0.0001）和凝血酶原酶复合物（FX; P = 0.003）水平显著较高，组织因子途径抑制物（TFPI; P = 0.033）水平较低。该数学模型生成时间依赖性预测，描述了主要促凝血因子和抑制剂的消耗、激活和相互作用，确定了MI患者和对照组之间以及男性和女性之间止血反应的不同模式。然而，在男性中，TF、FVIII、FIX和抑制剂TFPI导致病例和对照组之间的差异，而在女性中，FIB、FVIII和FIX对凝血酶生成的影响最大。我们还表明，根据预测的供体对抗凝治疗的反应，进一步的供体分层是可能的。我们认为，模型可能是有价值的，在提高我们的预测风险过早MI，复发风险和治疗效果。
Advancing understanding of key factors that determine the magnitude of the hemostatic response may facilitate the identification of individuals at risk of generating an occlusive thrombus as a result of an atherothrombotic event such as an acute Myocardial Infarction (MI). While fibrinogen levels are a recognized risk factor for MI, the association of thrombotic risk with other coagulation proteins is inconsistent. This is likely due to the complex balance of pro- and anticoagulant factors in any individual. We compared measured levels of pro- and anticoagulant proteins in plasma from 162 patients who suffered an MI at an early age (MI <50 y) and 186 age- and gender-matched healthy controls with no history of CAD. We then used the measurements from these individuals as inputs for an established mathematical model to investigate how small variations in hemostatic factors affect the overall amplitude of the hemostatic response and to identify differential key drivers of the hemostatic response in male and female patients and controls. Plasma from the MI patients contained significantly higher levels of Tissue Factor (P = 0.007), the components of the tenase (FIX and FVIII; P < 0.0001 for both) and the prothrombinase complexes (FX; P = 0.003), and lower levels of Tissue Factor Pathway Inhibitor (TFPI; P = 0.033) than controls. The mathematical model, which generates time-dependent predictions describing the depletion, activation, and interaction of the main procoagulant factors and inhibitors, identified different patterns of hemostatic response between MI patients and controls, and additionally, between males and females. Whereas, in males, TF, FVIII, FIX, and the inhibitor TFPI contribute to the differences seen between case and controls, and in females, FII, FVIII, and FIX had the greatest influence on the generation of thrombin. We additionally show that further donor stratification may be possible according to the predicted donor response to anticoagulant therapy. We suggest that modeling could be of value in enhancing our prediction of risk of premature MI, recurrent risk, and therapeutic efficacy.
登录
查看更多内容
影响因子：
5.4
作者：
Gaye B;Tafflet M;Arveiler D;Montaye M;Wagner A;Ruidavets JB;Kee F;Evans A;Amouyel P;Ferrieres J;Empana JP
通讯作者：
Empana JP
影响因子：
20.1
作者：
Diamond SL
通讯作者：
Diamond SL
影响因子：
3.5
作者：
Giannitsis, E;Siemens, HJ;Stierle, U
通讯作者：
Stierle, U
影响因子：
5.7
作者：
Burzotta, F;Paciaroni, K;Andreotti, F
通讯作者：
Andreotti, F
影响因子：
39
作者：
Cenko, Edina;Yoon, Jinsung;Bugiardini, Raffaele
通讯作者：
Bugiardini, Raffaele