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?

Affiliations
  • 1Department of Internal Medicine, Chosun University School of Medicine, Chosun University Hospital, Gwangju, Korea
  • 2Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA
  • 3Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, Korea


Figure

  • 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.


Cited by  1 articles

Beginning the Journey to Find Optimal Antithrombotic Regimens for Korean Patients with Atrial Fibrillation after Percutaneous Coronary Intervention
Sung Soo Kim, Hyun Kuk Kim
Korean Circ J. 2021;51(5):423-425.    doi: 10.4070/kcj.2021.0017.


Reference

1. Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010; 304:1350–1357. PMID: 20805624.
Article
2. Capodanno D, Bhatt DL, Eikelboom JW, et al. Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease. Nat Rev Cardiol. 2020; 17:242–257. PMID: 31953535.
Article
3. Gurbel PA, Fox KA, Tantry US, Ten Cate H, Weitz JI. Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease. Circulation. 2019; 139:2170–2185. PMID: 31034291.
Article
4. Jeong YH, Bliden KP, Shuldiner AR, Tantry US, Gurbel PA. Thrombin-induced platelet-fibrin clot strength: relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes. Thromb Haemost. 2014; 111:713–724. PMID: 24336898.
Article
5. Bae JS, Ahn JH, Jang JY, et al. The Impact of platelet-fibrin clot strength on occurrence and clinical outcomes of peripheral artery disease in patients with significant coronary artery disease. J Thromb Thrombolysis. 2020; [Epub ahead of print].
Article
6. Jeong YH, Bliden K, Ahn JH, et al. Viscoelastic properties of clot formation and their clinical impact in East Asian versus Caucasian patients with stable coronary artery disease: a COMPARE-RACE analysis. J Thromb Thrombolysis. 2020; [Epub ahead of print].
Article
7. Sanda T, Yoshimura M, Hyodo K, Ishii H, Yamashita T. Effects of long-term thrombin inhibition (dabigatran etexilate) on spontaneous thrombolytic activity during the progression of atherosclerosis in ApoE−/−–LDLR−/− double-knockout mice. Korean Circ J. 2020; 50:804–816. PMID: 32725990.
8. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020; 41:407–477. PMID: 31504439.
9. Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018; 391:219–229. PMID: 29132880.
10. Huo Y, Jeong YH, Gong Y, et al. 2018 update of expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Science Bulletin. 2019; 64:166–179.
Article
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