Korean Circ J.  2020 Sep;50(9):817-821. 10.4070/kcj.2020.0287.

Another Unmet Need against Residual Risk of Atherosclerotic Cardiovascular Disease: Can “Thrombin Pathway” Be a New Target for Therapy?

• Kim HK
• Tantry US
• Gurbel PA
• Jeong YH

• KMID: 2505737
• DOI: http://doi.org/10.4070/kcj.2020.0287

Figure

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  Figure 1 Role of factor Xa and thrombin in progression of atherothrombosis (modified from Capodanno et al. and Gurbel et al.).2)3)Factor Xa and thrombin contribute to atherothrombotic events through various mechanisms. Factor Xa (via PAR-1 and PAR-2) and thrombin (via PAR-1 and PAR-4) regulate the activation of endothelial cells, leukocytes, platelets, and vascular SMCs. PAR-mediated signaling are involved in endothelial cell activation and dysfunction, inflammatory process by production of pro-inflammatory cytokines and chemokines, and proliferation and apoptosis of vascular SMCs. Sustained inflammation in the lesion induces plaque instability and promotes plaque rupture. Thrombin is critical for platelet activation (via PAR-1 and PAR-4) and fibrin formation, which contribute to platelet-fibrin clot formation after plaque rupture. This experimental study showed that dabigatran has a potential to decrease progression of atherosclerotic plaque through reducing PFCS, and increasing spontaneous thrombolytic activity and eNOS.eNOS = endothelial nitric oxide synthase; PAI-1 = plasminogen activator inhibitor-1; PAR = protease-activated receptor; PFCS = platelet-fibrin clot strength; SMC = smooth muscle cell; TAFI = thrombin-activatable fibrinolysis inhibitor; TEG = thromboelastography.

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