Semin Thromb Hemost 2007; 33(2): 128-135
DOI: 10.1055/s-2007-969025
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Platelets and Endothelial Cells

Dorothea I. Siegel-Axel1 , Meinrad Gawaz1
  • 1Medizinische Klinik III, Eberhard Karls-Universität Tübingen, Tübingen, Germany
Further Information

Publication History

Publication Date:
06 March 2007 (online)

ABSTRACT

The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in industrial countries, is multifactorial. Atherogenesis, the development of atherosclerotic lesions, is initiated by a mechanical or functional injury of the endothelium. The function of the endothelium is influenced by multiple factors as a consequence of cell-cell interactions. Cell-cell communication between endothelial cells with platelets has only recently begun to receive systematic study. In recent years it has been established that platelet-endothelial interactions are involved at all stages of atherosclerotic disease. This article reviews the interactions between endothelial cells and platelets in the context of their role to initiate and accelerate atherothrombosis, as well as in acute thrombotic occlusion (e.g., at the site of atherosclerotic plaque rupture or subsequent to coronary angioplasty). From a mechanistic standpoint, platelets and endothelial cells communicate on multiple levels. Cross-talk may occur over a distance (paracrine signaling), via transient interactions (so-called give-and-go mechanism), or through receptor-mediated cell-cell adhesion. Platelets may release or transfer substances that influence endothelial cell function, and vice versa. Among many others, adhesion molecules, such as P-selectin (CD62P), are of special interest because of their role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. In addition to dietary, cholesterol and lipid lowering, and other pharmaceutical approaches, antiplatelet therapy plays an important part in the treatment of atherosclerosis and its multifactorial clinical manifestations. Understanding the specific interactions between platelets and the endothelium may lead to the development of novel therapeutic strategies.

REFERENCES

  • 1 Tan K T, Watson S P, Lip G Y. The endothelium and platelets in cardiovascular disease: potential targets for therapeutic intervention.  Curr Med Chem Cardiovasc Hematol Agents. 2004;  2 169-178
  • 2 McGregor L, Martin J, McGregor J L. Platelet-leukocyte aggregates and derived microparticles in inflammation, vascular remodelling and thrombosis.  Front Biosci. 2006;  11 830-837
  • 3 Weber C. Platelets and chemokines in atherosclerosis: partners in crime.  Circ Res. 2005;  96 612-616
  • 4 Cines D B, Pollak E S, Buck C A et al.. Endothelial cells in physiology and in the pathophysiology of vascular disorders.  Blood. 1998;  91 3527-3561
  • 5 Augustin H G, Kozian D H, Johnson R C. Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes.  Bioessays. 1994;  16 901-906
  • 6 Stouffer G A, Smyth S S. Effects of thrombin on interactions between beta3-integrins and extracellular matrix in platelets and vascular cells.  Arterioscler Thromb Vasc Biol. 2003;  23 1971-1978
  • 7 Harker L A, Roskos L K, Marzec U M et al.. Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers.  Blood. 2000;  95 2514-2522
  • 8 Warkentin T E, Aird W C, Rand J H. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome.  Hematology (Am Soc Hematol Educ Program). 2003;  497-519
  • 9 Sachais B S. Platelet-endothelial interactions in atherosclerosis.  Curr Atheroscler Rep. 2001;  3 412-416
  • 10 Li G, Sanders J M, Phan E T et al.. Arterial macrophages and regenerating endothelial cells express P-selectin in atherosclerosis-prone apolipoprotein E-deficient mice.  Am J Pathol. 2005;  167 1511-1518
  • 11 Gross P L, Aird W C. The endothelium and thrombosis.  Semin Thromb Hemost. 2000;  26 463-478
  • 12 Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease.  Curr Opin Lipidol. 2001;  12 383-389
  • 13 Tailor A, Granger D N. Role of adhesion molecules in vascular regulation and damage.  Curr Hypertens Rep. 2000;  2 78-83
  • 14 Sixma J J, Wester J. The hemostatic plug.  Semin Hematol. 1977;  14 265-299
  • 15 Langer H, Gawaz M. The coagulation cascade-clinical implications.  Herz. 2005;  30 170-175
  • 16 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8 1227-1234
  • 17 Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium.  Cardiovasc Res. 2004;  61 498-511
  • 18 Choi K. The hemangioblast: a common progenitor of hematopoietic and endothelial cells.  J Hematother Stem Cell Res. 2002;  11 91-101
  • 19 Denis C V. Molecular and cellular biology of von Willebrand factor.  Int J Hematol. 2002;  75 3-8
  • 20 Lin Y, Weisdorf D J, Solovey A et al.. Origins of circulating endothelial cells and endothelial outgrowth from blood.  J Clin Invest. 2000;  105 71-77
  • 21 Langer H, Gawaz M. The role of platelets for the pathophysiology of acute coronary syndromes.  Hamostaseologie. 2006;  26 114-118
  • 22 Ruggeri Z M. Platelet interactions with vessel wall components during thrombogenesis.  Blood Cells Mol Dis. 2006;  36 145-147
  • 23 Ruggeri Z M. Von Willebrand factor, platelets and endothelial cell interactions.  J Thromb Haemost. 2003;  1 1335-1342
  • 24 Massberg S, Gawaz M, Gruner S et al.. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo.  J Exp Med. 2003;  197 41-49
  • 25 Bennett J S. Novel platelet inhibitors.  Annu Rev Med. 2001;  52 161-184
  • 26 Turitto V T, Weiss H J, Zimmerman T S et al.. Factor VIII/von Willebrand factor in subendothelium mediates platelet adhesion.  Blood. 1985;  65 823-831
  • 27 Coller B S, Peerschke E I, Scudder L E et al.. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor.  Blood. 1983;  61 99-110
  • 28 Back L D, Radbill J R, Crawford D W. Analysis of pulsatile, viscous blood flow through diseased coronary arteries of man.  J Biomech. 1977;  10 339-353
  • 29 Andrews R K, Berndt M C. Platelet physiology and thrombosis.  Thromb Res. 2004;  114 447-453
  • 30 Gawaz M, Langer H, May A E. Platelets in inflammation and atherogenesis.  J Clin Invest. 2005;  115 3378-3384
  • 31 Steinhubl S R, Moliterno D J. The role of the platelet in the pathogenesis of atherothrombosis.  Am J Cardiovasc Drugs. 2005;  5 399-408
  • 32 Schwarz U R, Kobsar A L, Koksch M et al.. Inhibition of agonist-induced p42 and p38 mitogen-activated protein kinase phosphorylation and CD40 ligand/P-selectin expression by cyclic nucleotide-regulated pathways in human platelets.  Biochem Pharmacol. 2000;  60 1399-1407
  • 33 Lindemann S, Tolley N D, Eyre J R et al.. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control.  J Biol Chem. 2001;  276 33947-33951
  • 34 Weyrich A S, Lindemann S, Tolley N D et al.. Change in protein phenotype without a nucleus: translational control in platelets.  Semin Thromb Hemost. 2004;  30 491-498
  • 35 Eppley B L, Woodell J E, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing.  Plast Reconstr Surg. 2004;  114 1502-1508
  • 36 Nakazawa T, Yasuhara H, Shigematsu K et al.. Smooth muscle cell migration induced by shear-loaded platelets and endothelial cells. Enhanced platelet-derived growth factor production by shear-loaded platelets.  Int Angiol. 2000;  19 142-146
  • 37 Frenette P S, Moyna C, Hartwell D W et al.. Platelet-endothelial interactions in inflamed mesenteric venules.  Blood. 1998;  91 1318-1324
  • 38 Massberg S, Enders G, Matos F C et al.. Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo.  Blood. 1999;  94 3829-3838
  • 39 Romo G M, Dong J F, Schade A J et al.. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin.  J Exp Med. 1999;  190 803-814
  • 40 Frenette P S, Denis C V, Weiss L et al.. P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo.  J Exp Med. 2000;  191 1413-1422
  • 41 Gawaz M, Neumann F J, Dickfeld T et al.. Vitronectin receptor (alpha(v)beta3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction.  Circulation. 1997;  96 1809-1818
  • 42 Langer H, May A E, Bultmann A et al.. ADAM 15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation.  Thromb Haemost. 2005;  94 555-561
  • 43 Herren B, Raines E W, Ross R. Expression of a disintegrin-like protein in cultured human vascular cells and in vivo.  FASEB J. 1997;  11 173-180
  • 44 Horiuchi K, Weskamp G, Lum L et al.. Potential role for ADAM15 in pathological neovascularization in mice.  Mol Cell Biol. 2003;  23 5614-5624
  • 45 Lindemann S, Tolley N D, Dixon D A et al.. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis.  J Cell Biol. 2001;  154 485-490
  • 46 May A E, Kalsch T, Massberg S et al.. Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells.  Circulation. 2002;  106 2111-2117
  • 47 Slupsky J R, Kalbas M, Willuweit A et al.. Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40.  Thromb Haemost. 1998;  80 1008-1014
  • 48 Gawaz M, Neumann F J, Dickfeld T et al.. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells.  Circulation. 1998;  98 1164-1171
  • 49 May A E, Kalsch T, Massberg S et al.. Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells.  Circulation. 2002;  106 2111-2117
  • 50 Inwald D P, McDowall A, Peters M J et al.. CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation.  Circ Res. 2003;  92 1041-1048
  • 51 Frenette P S, Johnson R C, Hynes R O et al.. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin.  Proc Natl Acad Sci USA. 1995;  92 7450-7454
  • 52 Andre P, Denis C V, Ware J et al.. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins.  Blood. 2000;  96 3322-3328
  • 53 Johnson R C, Chapman S M, Dong Z M et al.. Absence of P-selectin delays fatty streak formation in mice.  J Clin Invest. 1997;  99 1037-1043
  • 54 Dong Z M, Brown A A, Wagner D D. Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice.  Circulation. 2000;  101 2290-2295
  • 55 Burger P C, Wagner D D. Platelet P-selectin facilitates atherosclerotic lesion development.  Blood. 2003;  101 2661-2666
  • 56 Massberg S, Brand K, Gruner S et al.. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation.  J Exp Med. 2002;  196 887-896
  • 57 Theilmeier G, Michiels C, Spaepen E et al.. Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia.  Blood. 2002;  99 4486-4493
  • 58 Cherian P, Hankey G J, Eikelboom J W et al.. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes.  Stroke. 2003;  34 2132-2137
  • 59 Berndt M C. Induction of platelet-endothelial interactions in postcapillary venules in hypercholesterolemia: critical role of P-selectin.  Arterioscler Thromb Vasc Biol. 2003;  23 525-527
  • 60 Berger G, Hartwell D W, Wagner D D. P-selectin and platelet clearance.  Blood. 1998;  92 4446-4452
  • 61 Davi G, Romano M, Mezzetti A et al.. Increased levels of soluble P-selectin in hypercholesterolemic patients.  Circulation. 1998;  97 953-957
  • 62 Andre P, Hartwell D, Hrachovinova I et al.. Pro-coagulant state resulting from high levels of soluble P-selectin in blood.  Proc Natl Acad Sci USA. 2000;  97 13835-13840
  • 63 Massberg S, Schulz C, Gawaz M. Role of platelets in the pathophysiology of acute coronary syndrome.  Semin Vasc Med. 2003;  3 147-162
  • 64 Neumann F J, Blasini R, Schmitt C et al.. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction.  Circulation. 1998;  98 2695-2701

Meinrad GawazM.D. 

Medizinische Klinik III, Eberhard Karls Universität Tübingen

Otfried-Müller-Str. 10, D-72076 Tübingen, Germany

Email: meinrad.gawaz@med.uni-tuebingen.de