title: Re-evaluation of the anticoagulant properties of high-density lipoprotein-brief report.
abstract: OBJECTIVE
  This study was conducted to resolve the striking controversy between our previous report that high-density lipoprotein (HDL) enhances activated protein C (APC)/protein S anticoagulant actions and a subsequent, contradicting report that HDL lacks this activity.
  
  
  RESULTS
  When fresh HDL preparations from 2 laboratories were subjected to Superose 6 column chromatography, fractions containing HDL-enhanced APC:protein S anticoagulant actions in clotting assays, thereby validating our previous report. Moreover, the ability of HDL to enhance the anticoagulant actions of APC:protein S was neutralized by anti-apoAI antibodies, further indicating that the activity is because of HDL particles and not because of contaminating phospholipid vesicles. Density gradient subfractionation studies of HDL showed that large HDL subfractions (densities between 1.063 and 1.125 g/mL) contained the APC:protein S-enhancing activity. Fresh HDL stored at 4°C gradually lost its anticoagulant enhancing activity for 14 days, indicating moderate instability in this activity of purified HDL.
  
  
  CONCLUSIONS
  These studies conclusively demonstrate that freshly prepared HDL fractions possess anticoagulant activity. Fractions from Superose 6 columns that contain HDL reproducibly enhance APC:protein S anticoagulant activity, consistent with the hypothesis that HDL has antithrombotic activity and with the observation that low HDL levels are found in male venous thrombosis patients. Understanding the basis for this activity could lead to novel therapeutic approaches to regulate venous thrombosis.
authors.affiliation: From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (J.A.F., H.D., J.H.G.); and Department of Medicine, University of California San Diego (C.L.B., J.L.W., J.H.G.).
authors.forename: Jose A
authors.initials: JA
authors.lastname: Fernandez
authors.affiliation: From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (J.A.F., H.D., J.H.G.); and Department of Medicine, University of California San Diego (C.L.B., J.L.W., J.H.G.).
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Deguchi
authors.affiliation: From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (J.A.F., H.D., J.H.G.); and Department of Medicine, University of California San Diego (C.L.B., J.L.W., J.H.G.).
authors.forename: Carole L
authors.initials: CL
authors.lastname: Banka
authors.affiliation: From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (J.A.F., H.D., J.H.G.); and Department of Medicine, University of California San Diego (C.L.B., J.L.W., J.H.G.).
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA (J.A.F., H.D., J.H.G.); and Department of Medicine, University of California San Diego (C.L.B., J.L.W., J.H.G.). jgriffin@scripps.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Griffin
mesh_terms: D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002499:Centrifugation, Density Gradient; D002845:Chromatography / Q000379:methods; D003080:Cold Temperature; D005343:Fibrinolytic Agents / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000494:pharmacology*; D011486:Protein C / Q000378:metabolism; D011489:Protein Denaturation; D017293:Protein S / Q000378:metabolism; D055550:Protein Stability; D013997:Time Factors
chemical_list: C505693:APOA1 protein, human; D000925:Anticoagulants; D016632:Apolipoprotein A-I; D005343:Fibrinolytic Agents; D008075:Lipoproteins, HDL; D011486:Protein C; D017293:Protein S
keywords: high-density lipoproteins; protein C; protein S; thromboplastin; thrombosis