Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia
High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagu...
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Published in | Thrombosis and haemostasis Vol. 77; no. 2; p. 303 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
1997
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Abstract | High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachidonate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia. |
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AbstractList | High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachidonate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia. |
Author | ten Cate, J W Lerch, P G Doran, J E Pajkrt, D van der Poll, T van Deventer, S J Illi, M Arnet, B van den Ende, A Levi, M |
Author_xml | – sequence: 1 givenname: D surname: Pajkrt fullname: Pajkrt, D organization: Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands – sequence: 2 givenname: P G surname: Lerch fullname: Lerch, P G – sequence: 3 givenname: T surname: van der Poll fullname: van der Poll, T – sequence: 4 givenname: M surname: Levi fullname: Levi, M – sequence: 5 givenname: M surname: Illi fullname: Illi, M – sequence: 6 givenname: J E surname: Doran fullname: Doran, J E – sequence: 7 givenname: B surname: Arnet fullname: Arnet, B – sequence: 8 givenname: A surname: van den Ende fullname: van den Ende, A – sequence: 9 givenname: J W surname: ten Cate fullname: ten Cate, J W – sequence: 10 givenname: S J surname: van Deventer fullname: van Deventer, S J |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/9157586$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Adult Blood Coagulation - drug effects Cross-Over Studies Cytokines - blood Double-Blind Method Endotoxemia - blood Endotoxemia - drug therapy Endotoxins - adverse effects Endotoxins - antagonists & inhibitors Fibrinolysis - drug effects Humans Lipopolysaccharides - antagonists & inhibitors Lipoproteins, HDL - pharmacology Lipoproteins, HDL - therapeutic use Male Peptide Fragments - analysis Plasminogen Activator Inhibitor 1 - analysis Platelet Activation - drug effects Platelet Aggregation Prothrombin - analysis |
Title | Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia |
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