title: High-density lipoprotein as a modulator of platelet and coagulation responses.
abstract: Platelets and coagulation factors are involved in the process of haemostasis, which ensures undisturbed blood flow upon vessel wall damage. However, excessive platelet aggregation and/or coagulation may lead to arterial or venous thrombosis. Pro-atherogenic lipoproteins, including native and oxidized low-density lipoprotein (LDL), are associated with an increased susceptibility to thrombosis. In contrast, numerous epidemiological studies have established an inverse correlation between high-density lipoprotein (HDL) levels and the risk for thrombosis. In addition to its role in reverse cholesterol transport, HDL also interacts with platelets, the coagulation cascade, and the vascular endothelium. Native HDL prevents platelet hyperreactivity by limiting intraplatelet cholesterol overload, as well as by modulating platelet signalling pathways after binding platelet HDL receptors such as scavenger receptor class B type I (SR-BI) and apoER2'. The antithrombotic properties of native HDL are also related to the suppression of the coagulation cascade and stimulation of clot fibrinolysis. Furthermore, HDL stimulates the endothelial production of nitric oxide and prostacyclin, which are potent inhibitors of platelet activation. Thus, HDL's antithrombotic actions are multiple and therefore, raising HDL may be an important therapeutic strategy to reduce the risk of arterial and venous thrombosis.
authors.affiliation: Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300RA Leiden, The Netherlands Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van der Stoep
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Suzanne J A
authors.initials: SJ
authors.lastname: Korporaal
authors.affiliation: Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300RA Leiden, The Netherlands m.eck@lacdr.leidenuniv.nl.
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D015539:Platelet Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins
keywords: Arterial thrombosis; Coagulation; High-density lipoprotein; Platelets; Venous thrombosis