Shilin He

Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases.

It is widely recognized that thrombosis is the major event in the evolution of acute myocardial infarction (AMI) and acute ischemic stroke (AIS). But the contribution of coagulation factors to the development of ischemic arterial diseases is still not clearly established. The goal of this study was to establish the possible relationship between coagulation factors as well as anticoagulant and the onset of AMI and AIS. The study population consisted of 69 patients with AMI and 71 with AIS as well as 50 age-matched healthy volunteers. Compared with the control group, plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activities and both TF and TFPI antigens were significantly higher in the AMI group; plasma TF activity and antigen in AIS group were significantly increased, but the activity and antigen of plasma TFPI were significantly decreased in the AIS group. Plasma FVII coagulation (FVII:C) activity was markedly higher in patients with AIS, but not statistically different to the control in patients with AMI. FVIII coagulation (FVIII:C) activity was remarkably higher in patients with AMI but slightly lower than the control in patients with AIS. In the AMI and AIS groups, prothrombin activity and clottable fibrinogen were significantly higher and plasma antithrombin III activity was remarkably lower than the control. The results suggested that during the onset of AMI and AIS, the initiation of TF pathway would be associated with the thrombotic events and that the blood be in hypercoagulable state. But the changes of FVII:C, TFPI and FVIII:C in AMI are different from those in AIS.

Factor XI: hemostasis, thrombosis, and antithrombosis.

Coagulation factor FXI (FXI), a plasma serine protease zymogen, has important roles in both intrinsic and extrinsic coagulation pathways and bridges the initiation and amplification phases of plasmatic hemostasis. Recent studies have provided new insight into the molecular structure and functional features of FXI and have demonstrated distinct structural and biological differences between activated factor XII (FXIIa)-mediated FXI activation and tissue factor/thrombin-mediated FXI activation. The former is important in thrombosis; the latter is more essential in hemostasis. Activated partial thromboplastin tine (aPTT) artificially reflects FXIIa-initiated intrinsic coagulation pathway in vitro. Conversely, FXIIa-inhibited diluted thromboplastin time assay may reflect tissue factor/thrombin-mediated FXI activation in vivo. Further explication of the genetic mutations of FXI deficiency has improved the understanding of the structure-function relationship of FXI. Besides its procoagulant activity, the antifibrinolytic activity of FXI was well documented in a wealth of literature. Finally, the new emerging concept of inhibiting FXI as a novel antithrombotic approach with an improved benefit-risk ratio has been supported through observations from human FXI deficiency and various animal models. Large- and small-molecule FXI inhibitors have shown promising antithrombotic effects. The present review summarizes the recent advancements in the molecular physiology of FXI and the molecular pathogenesis of FXI deficiency and discusses the evidence and progress of FXI-targeting antithrombotics development.

Effects of cinnamic acid on expression of tissue factor induced by TNFα in endothelial cells and its mechanisms

Background: To observe the effects of cinnamic acid (CINN) on the expression of tissue factor (TF) induced by tumor necrosis factor alpha (TNFα) in human umbilical vein endothelium‐derived cell line (ECV304) and the related mechanisms. Methods: Cellular TF activity was determined with 1‐stage clotting assay in the presence or absence of anti‐TF antibody or DEGR‐VIIa. TF mRNA was examined by semi‐quantitative reverse transcription polymerase chain reaction (RT‐PCR). I‐κB was measured by Western blot analysis. Immunohistochemical analysis was performed to evaluate the activation of NF‐κB. Results: CINN (500 μg/mL) significantly decreased the TF activity in ECV304 induced by TNFα (1,000 U/mL) (p< 0.01) in a concentration‐dependent fashion (r = −0.953, p < 0.05). CINN also inhibited the expression of TF mRNA induced by TNFα. Immunohistochemical analysis demonstrated NF‐κB translocation from the cytoplasm to the nucleus, and Western blot analysis showed I‐?B decrement in cytoplasm after treatment of endothelial cells with TNFα. CINN diminished these changes induced by TNFα. Conclusion: CINN is able to attenuate TNFα‐induced TF expression of vascular endothelial cells by inhibiting NF‐κB activation.