Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques
- PMID: 32166823
- PMCID: PMC7317428
- DOI: 10.1111/pin.12921
Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques
Abstract
Atherothrombosis is a leading cause of cardiovascular mortality and morbidity worldwide. The underlying mechanisms of atherothrombosis comprise plaque disruption and subsequent thrombus formation. Arterial thrombi are thought to mainly comprise aggregated platelets as a result of high blood velocity. However, thrombi that develop on disrupted plaques comprise not only aggregated platelets, but also large amounts of fibrin, because plaques contain large amount of tissue factor that activate the coagulation cascade. Since not all thrombi grow large enough to occlude the vascular lumen, the propagation of thrombi is also critical in the onset of adverse vascular events. Various factors such as vascular wall thrombogenicity, local hemorheology, systemic thrombogenicity and fibrinolytic activity modulate thrombus formation and propagation. Although the activation mechanisms of platelets and the coagulation cascade have been intensively investigated, the underlying mechanisms of occlusive thrombus formation on disrupted plaques remain obscure. Pathological findings derived from humans and animal models of human atherothrombosis have uncovered pathophysiological processes during thrombus formation and propagation after plaque disruption, and novel factors have been identified that modulate the activation of platelets and the coagulation cascade. These findings have also provided insights into the development of novel drugs for atherothrombosis.
Keywords: atherothrombosis; blood flow; coagulation factor; platelet; vasoconstriction.
© 2020 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g004.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g005.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g006.gif)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g007.gif)
![Figure 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g008.gif)
![Figure 9](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7317428/bin/PIN-70-309-g009.gif)
Similar articles
-
Thrombus Formation and Propagation in the Onset of Cardiovascular Events.J Atheroscler Thromb. 2018 Aug 1;25(8):653-664. doi: 10.5551/jat.RV17022. Epub 2018 Jun 9. J Atheroscler Thromb. 2018. PMID: 29887539 Free PMC article. Review.
-
Underlying mechanisms of thrombus formation/growth in atherothrombosis and deep vein thrombosis.Pathol Int. 2023 Feb;73(2):65-80. doi: 10.1111/pin.13305. Epub 2023 Jan 4. Pathol Int. 2023. PMID: 36598039 Review.
-
Thrombosis formation on atherosclerotic lesions and plaque rupture.J Intern Med. 2014 Dec;276(6):618-32. doi: 10.1111/joim.12296. Epub 2014 Sep 25. J Intern Med. 2014. PMID: 25156650 Review.
-
Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.Thromb Haemost. 2018 Feb;118(2):229-250. doi: 10.1160/TH17-07-0492. Epub 2018 Jan 29. Thromb Haemost. 2018. PMID: 29378352 Free PMC article.
-
Tissue factor and atherothrombosis.Curr Pharm Des. 2015;21(9):1152-7. doi: 10.2174/1381612820666141013154946. Curr Pharm Des. 2015. PMID: 25312727 Review.
Cited by
-
Atherosclerosis originating from childhood: Specific features.J Biomed Res. 2024 May 22;38(3):233-240. doi: 10.7555/JBR.37.20230198. J Biomed Res. 2024. PMID: 38777340 Free PMC article.
-
Synthetic Haemostatic Sealants: Effectiveness, Safety, and In Vivo Applications.Pharmaceuticals (Basel). 2024 Feb 23;17(3):288. doi: 10.3390/ph17030288. Pharmaceuticals (Basel). 2024. PMID: 38543074 Free PMC article.
-
C-type lectin-like receptor 2: roles and drug target.Thromb J. 2024 Mar 19;22(1):27. doi: 10.1186/s12959-024-00594-8. Thromb J. 2024. PMID: 38504248 Free PMC article. Review.
-
CB2 Cannabinoid Receptor as a Potential Target in Myocardial Infarction: Exploration of Molecular Pathogenesis and Therapeutic Strategies.Int J Mol Sci. 2024 Jan 30;25(3):1683. doi: 10.3390/ijms25031683. Int J Mol Sci. 2024. PMID: 38338960 Free PMC article. Review.
-
Detection of monosodium urate depositions and atherosclerotic plaques in the cardiovascular system by dual-energy computed tomography.Heliyon. 2024 Jan 17;10(2):e24548. doi: 10.1016/j.heliyon.2024.e24548. eCollection 2024 Jan 30. Heliyon. 2024. PMID: 38304777 Free PMC article.
References
-
- Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657–71. - PubMed
-
- Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions: Experimental evidence and potential clinical implications. Circulation 1989; 80: 198–205. - PubMed
-
- Coller BS. Anti‐GPIIb/IIIa drugs: Current strategies and future directions. Thromb Haemost 2001; 86: 427–43. - PubMed
-
- Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: The GUSTO IV‐ACS randomised trial. GUSTO IV‐ACS Investigators. Lancet 2001; 357: 1915–24. - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical