Reconstituted High Density Lipoprotein (rHDL) Modulates Platelet Activity In Vitro and Ex Vivo

Peter G. Lerch; Martin O. Spycher; Jan E. Doran

doi:10.1055/s-0037-1615194

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(02): 316-320
DOI: 10.1055/s-0037-1615194

Rapid Communication

Schattauer GmbH

Reconstituted High Density Lipoprotein (rHDL) Modulates Platelet Activity In Vitro and Ex Vivo

Peter G. Lerch

¹From the ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Martin O. Spycher

¹From the ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

,

Jan E. Doran

¹From the ZLB Central Laboratory, Blood Transfusion Service SRC, Bern, Switzerland

› Author Affiliations

Abstract

Summary

A reconstituted high density lipoprotein (rHDL) prepared for clinical use was tested for its influence on platelet activity modulated by various stimuli. In a first series of in vitro experiments, rHDL was added to blood in a concentration series, and platelet rich plasma (PRP) was isolated. Platelets were stimulated with arachidonic acid, collagen, epinephrine or ADP, and platelet aggregation was assessed. rHDL mediated a dose dependent inhibition of the platelet activity. With purified platelets rHDL inhibited the release reaction induced by collagen, but not by thrombin, as measured by CD62P (P-Selectin) expression on the plasma membrane. Ex vivo experiments were performed with PRP from volunteers, previously infused with 25 mg rHDL/kg body weight and 40 mg rHDL/kg body weight, respectively. Platelet activity in PRP was assessed before, and up to 30 h after the end of the rHDL infusion. A transient inhibition of the platelet aggregation induced by arachidonic acid and collagen was observed which was more pronounced in the group receiving 40 mg rHDL/kg body weight. In both groups of experiments, in vitro and ex vivo, the inhibition of the platelet activity was also dependent on the stimulus used.

Full Text

References

References
1 Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease and death. The Framingham Study. Arch Intern Med 1981; 141: 1128-31.
2 Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1975; I: 16-9.
3 Surya II, Akkerman J-WN. The influence of lipoproteins on blood platelets. Am Heart J 1993; 125: 272-5.
4 Levine DM, Parker TS, Donnelly TM, Walsh A, Rubin AL. In vivo protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci USA 1993; 90: 12040-4.
5 Hubsch AP, Powell FS, Lerch PG, Doran JE. A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. Circ Shock 1993; 40: 14-23.
6 Lerch PG, Förtsch V, Hodler G, Bolli R. Production and characterization of a reconstituted high density lipoprotein (rHDL) for therapeutic applications. Vox Sang 1996; 71: 155-64.
7 Lerch PG, Morgenthaler J-J, Peitsch MC, Friedli H, Hodler G, Doran JE, Isliker H, Heiniger H-J. Isolation and properties of apolipoprotein A for therapeutic use. Protides Biol Fluid Proc Colloq 1989; 36: 409-16.
8 Desai K, Bruckdorfer KR, Hutton RA, Owen JS. Binding of apoE-rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation. J Lipid Res 1989; 30: 831-40.
9 Higashihara M, Kinoshita M, Teramoto T, Kume S, Korokawa K. The role of apoE in inhibitory effects of apoE-rich HDL on platelet function. FEBS Lett 1991; 282: 82-6.
10 Riddell DR, Owen JS. Inhibition of ADP-induced platelet aggregation by apoE is not mediated by membrane cholesterol depletion. Thromb Res 1995; 80: 499-508.
11 Koller E, Koller F, Binder BR. Purification and identification of the lipoprotein-binding proteins from human blood platelet membrane. J Biol Chem 1989; 264: 12412-8.
12 Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GP Ia/IIa and an indirect interaction with GP IIb/IIIa mediated by adhesive proteins. Blood 1986; 74: 182-92.
13 Sugatani J, Miwa M, Komiyama Y, Ito S. High-density lipoprotein inhibits the synthesis of platelet-activating factor in human vascular endothelial cells. J Lipid Mediat Cell Signal 1996; 13: 73-88.
14 Benveniste J, Nunez D, Duriez P, Korth R, Bidault J, Fruchart JC. Preformed PAF-acether and lyso PAF-acether are bound to blood lipo-proteins. FEBS Lett 1988; 226: 371-6.
15 Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C. Serum Prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). Novel function of Apo A-I, J Clin Invest 1988; 82: 803-7.
16 Tamagaki T, Sawada S, Imamura H, Tada Y, Yamasaki S, Toratani A, Sato T, Komatsu S, Akamats N, Yamagami M, Kobayashi K, Kato K, Yamamoto K, Shirai K, Yamada K, Higaki T, Nakagawa K, Tsuji H, Nakagawa M. Effects of high-density lipoproteins on intracellular pH and proliferation of human vascular endothelial cells. Atherosclerosis 1996; 123: 73-82.
17 Chen LY, Mehta JL. Inhibitory effect of high-density lipoprotein on platelet function is mediated by increase in nitric oxide synthase activity in platelets. Life Sci 1994; 55: 1815-21.
18 Ross R. The pathogenesis of atherosclerosis – an update. N Engl J Med 1986; 314: 488-500.
19 Curtiss LK, Dyer CA, Banka CL, Black AS. Platelet-mediated foam cell formation in atherosclerosis. Clin Invest Med 1990; 13: 189-95.
20 Salky N, Dugdale M. Platelet abnormalities in ischemic heart disease. Am J Cardiol 1973; 32: 612-7.
21 Terres W, Lund GK, Hübner A, Ehlert A, Reuter H, Hamm CW. Endogenous tissue plasminagen activator and platelet reactivity as risk factors for reocclusion after recanalization of chronic total coronary occlusions. Am Heart J 1995; 130: 711-6.
22 Ameli S, Hultgardh-Nilsson A, Cercek B, Shah PK, Forrester JS, Ageland H, Nilsson J. Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits. Circulation 1994; 90: 1935-41.
23 Hubsch AP, Casas AT, Doran JE. Protective effects of reconstituted high-density lipoprotein in rabbit gram-negative bacteremia models. J Lab Clin Med 1995; 126: 548-58.
24 Quezado ZMN, Natanson C, Banks SM, Alling DW, Koey CA, Danner RL, Elin RJ, Hosseini JM, Parker TS, Levine DM, Rubin AL, Hoffman WD. Therapeutic trial of reconstituted human high-density lipoprotein in a canine model of gram-negative septic shock. J Pharmacol Exp Therap 1995; 272: 604-11.
25 Casas AT, Hubsch AP, Carter BC, Doran JE. Reconstituted high-density lipoprotein reduces LPS-stimulated TNFα. J Surg Res 1995; 59: 544-52.
26 Cué JI, DiPiro JT, Brunner LJ, Doran JE, Blankenship ME, Mansberger AR, Hawkins ML. Reconstituted high density lipoprotein inhibits physiologic and tumor necrosis factor response to lipopolysaccharide in rabbits. Arch Surg 1994; 129: 193-7.
27 Pajkrt D, Doran JE, Koster F, Lerch PG, Arnet B, van der Poll T, ten Cate JW, van Deventer SJH. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 1996; 184: 1601-8.
28 Henn V, Slupsky JR, Gräfe M, Anagnostopoulos I, Förster R, Müller Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
29 Klinger MHF. Platelets and inflammation. Anat Embryol 1997; 196: 1-11.
30 Faint RW. Platelet-neutrophil interactions: Their significance. Blood Rev 1992; 6: 83-91.
31 Pajkrt D, Lerch PG, van der Poll T, Levi M, Illi M, Doran JE, Arnet B, van den Ende A, ten Cate JW, van Deventer SJH. Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia. Thromb Haemost 1996; 77: 303-7.