Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues
Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing a highly polymorphic apolipoprotein(a) [apo(a)] homologous in > 80% to plasminogen, was identified as a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, found in about 20% o...
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Termedia Publishing House
2024-12-01
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| Series: | Archives of Medical Science |
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| author | Małgorzata Konieczyńska Joanna Natorska Michał Ząbczyk Anetta Undas |
| author_facet | Małgorzata Konieczyńska Joanna Natorska Michał Ząbczyk Anetta Undas |
| author_sort | Małgorzata Konieczyńska |
| collection | DOAJ |
| description | Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing a highly polymorphic apolipoprotein(a) [apo(a)] homologous in > 80% to plasminogen, was identified as a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, found in about 20% of Europeans, are strongly linked to higher rates of myocardial infarction, major adverse cardiac events, accelerated plaque progression, ischemic stroke (especially in younger adults), and calcific aortic valve disease. However, its role in venous thromboembolism, including atypical locations like cerebral and retinal vein thrombosis, remains controversial despite several shared mechanisms underlying arterial and venous thromboembolism. The most robust evidence supports antifibrinolytic properties of elevated Lp(a), particularly smaller apo(a) isoforms, which inhibit plasminogen activation mainly by interacting with the tissue-type plasminogen activator, plasminogen, and fibrin. Other prothrombotic mechanisms include increased synthesis of plasminogen activator inhibitor (PAI-1), formation of denser fibrin networks composed of thinner fibers, less susceptible to lysis, increased platelet activation, enhanced oxidation of phospholipids leading to a low-grade proinflammatory state, upregulated tissue factor expression, and suppression of tissue factor pathway inhibitor. Targeted Lp(a) lowering therapies are currently being tested in randomized clinical trials and could potentially have clinically relevant antithrombotic effects, evidenced by the reduced risk of thromboembolism. This review summarizes the available data on the prothrombotic and antifibrinolytic actions of Lp(a), along with clinical evidence for the increased risk of thromboembolic events related to elevated Lp(a). It also introduces new concepts to explain discrepant clinical results regarding venous events, highlighting the impact of oxidized phospholipids on a prothrombotic state under conditions of high Lp(a). |
| format | Article |
| id | doaj-art-1c4ac8e406ea4e159a48be682e47cc55 |
| institution | Kabale University |
| issn | 1734-1922 1896-9151 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Archives of Medical Science |
| spelling | doaj-art-1c4ac8e406ea4e159a48be682e47cc552025-01-27T10:45:12ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512024-12-012061770178310.5114/aoms/197357197357Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issuesMałgorzata Konieczyńska0https://orcid.org/0000-0001-6834-6129Joanna Natorska1Michał Ząbczyk2https://orcid.org/0000-0003-1762-308XAnetta Undas3https://orcid.org/0000-0003-3716-1724Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, PolandDepartment of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, PolandDepartment of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, PolandDepartment of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, PolandLipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing a highly polymorphic apolipoprotein(a) [apo(a)] homologous in > 80% to plasminogen, was identified as a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, found in about 20% of Europeans, are strongly linked to higher rates of myocardial infarction, major adverse cardiac events, accelerated plaque progression, ischemic stroke (especially in younger adults), and calcific aortic valve disease. However, its role in venous thromboembolism, including atypical locations like cerebral and retinal vein thrombosis, remains controversial despite several shared mechanisms underlying arterial and venous thromboembolism. The most robust evidence supports antifibrinolytic properties of elevated Lp(a), particularly smaller apo(a) isoforms, which inhibit plasminogen activation mainly by interacting with the tissue-type plasminogen activator, plasminogen, and fibrin. Other prothrombotic mechanisms include increased synthesis of plasminogen activator inhibitor (PAI-1), formation of denser fibrin networks composed of thinner fibers, less susceptible to lysis, increased platelet activation, enhanced oxidation of phospholipids leading to a low-grade proinflammatory state, upregulated tissue factor expression, and suppression of tissue factor pathway inhibitor. Targeted Lp(a) lowering therapies are currently being tested in randomized clinical trials and could potentially have clinically relevant antithrombotic effects, evidenced by the reduced risk of thromboembolism. This review summarizes the available data on the prothrombotic and antifibrinolytic actions of Lp(a), along with clinical evidence for the increased risk of thromboembolic events related to elevated Lp(a). It also introduces new concepts to explain discrepant clinical results regarding venous events, highlighting the impact of oxidized phospholipids on a prothrombotic state under conditions of high Lp(a).https://www.archivesofmedicalscience.com/Lipoprotein-a-and-thromboembolism-current-state-of-knowledge-and-unsolved-issues,197357,0,2.htmlarterial thromboembolismfibrinolysislipoprotein(a)strokethrombosis |
| spellingShingle | Małgorzata Konieczyńska Joanna Natorska Michał Ząbczyk Anetta Undas Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues Archives of Medical Science arterial thromboembolism fibrinolysis lipoprotein(a) stroke thrombosis |
| title | Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues |
| title_full | Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues |
| title_fullStr | Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues |
| title_full_unstemmed | Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues |
| title_short | Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues |
| title_sort | lipoprotein a and thromboembolism current state of knowledge and unsolved issues |
| topic | arterial thromboembolism fibrinolysis lipoprotein(a) stroke thrombosis |
| url | https://www.archivesofmedicalscience.com/Lipoprotein-a-and-thromboembolism-current-state-of-knowledge-and-unsolved-issues,197357,0,2.html |
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