Download PDF
Thromb Haemost 2004; 91(02): 345-353
DOI: 10.1160/TH03-05-0294
Platelets and Blood Cells
Schattauer GmbH

Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus

Olivier Morel
1   Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg
2   Institut d’Hématologie et d’Immunologie, Université Louis Pasteur, Strasbourg
,
Bénédicte Hugel
2   Institut d’Hématologie et d’Immunologie, Université Louis Pasteur, Strasbourg
,
Laurence Jesel
1   Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg
,
François Lanza
3   Etablissement Français du Sang-Alsace
4   U. 311 INSERM, Strasbourg
,
Marie-Pierre Douchet
1   Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg
,
Michel Zupan
1   Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg
,
Michel Chauvin
1   Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg
,
Jean-Pierre Cazenave
3   Etablissement Français du Sang-Alsace
4   U. 311 INSERM, Strasbourg
,
Jean-Marie Freyssinet
2   Institut d’Hématologie et d’Immunologie, Université Louis Pasteur, Strasbourg
5   U. 143 INSERM, Hôpital de Bicêtre
,
Florence Toti
2   Institut d’Hématologie et d’Immunologie, Université Louis Pasteur, Strasbourg
5   U. 143 INSERM, Hôpital de Bicêtre
6   Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France
› Author AffiliationsFinancial support: This work was supported by institutional grants from the Groupe pour l’Enseignement et la Recherche Médicale (GERM) Schiltigheim, France, the Institut National de la Santé et de la Recherche Médicale (INSERM), and the Université Louis Pasteur, Strasbourg, France.
Further Information

Publication History

Received 15 May 2003

Accepted after resubmission 05 January 2003

Publication Date:
01 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardiovascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 ± 4.8 vs. 12.3 ± 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.

Keywords

Apoptosis - thrombosis - atherosclerosis - endothelium damage - platelet stimulation - sCD40 Ligand
 

  • References

  • 1 Aupeix K, Hugel B, Martin T. et al. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J Clin Invest 1997; 99: 1546-54.
    CrossrefPubMedSearch in Google Scholar
  • 2 VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59: 277-87.
    CrossrefPubMedSearch in Google Scholar
  • 3 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-3.
    CrossrefPubMedSearch in Google Scholar
  • 4 Mallat Z, Tedgui A. Current perspective on the role of apoptosis in atherothrombotic disease. Circ Res 2001; 88: 998-1003.
    CrossrefPubMedSearch in Google Scholar
  • 5 Fukumoto H, Naito Z, Asano G, Aramaki T. Immunohistochemical and morphometric evaluations of coronary atherosclerotic plaques associated with myocardial infarction and diabetes mellitus. J Atheroscler Thromb 1998; 05: 29-35.
    CrossrefPubMedSearch in Google Scholar
  • 6 Farb A, Burke AP, Tang AL. et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354-63.
    CrossrefPubMedSearch in Google Scholar
  • 7 Zwaal RF, Schroit AJ. Pathophysiologic implications of membrane phospholipid assymetry in blood cells. Blood 1997; 89: 1121-32.
    PubMedSearch in Google Scholar
  • 8 Rauch U, Nemerson Y. Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000; 10: 139-43.
    CrossrefPubMedSearch in Google Scholar
  • 9 Bach R, Rifkin DB. Expression of tissue factor procoagulant activity: regulation by cytosolic calcium. Proc Natl Acad Sci U S A 1990; 87: 6995-9.
    CrossrefPubMedSearch in Google Scholar
  • 10 Barry OP, FitzGerald GA. Mechanisms of cellular activation by platelet microparticles. Thromb Haemost 1999; 82: 794-800.
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Freyssinet JM, Toti F, Hugel B. et al. Apoptosis in vascular disease. Thromb Haemost 1999; 82: 727-35.
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Sabatier F, Darmon P, Hugel B. et al. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes 2002; 51: 2840-5.
    CrossrefPubMedSearch in Google Scholar
  • 13 Omoto S, Nomura S, Shouzu A. et al. Detection of monocyte-derived microparticles in patients with Type II diabetes mellitus. Diabetologia 2002; 45: 550-5.
    CrossrefPubMedSearch in Google Scholar
  • 14 Frustaci A, Kajstura J, Chimenti C. et al. Myocardial cell death in human diabetes. Circ Res 2000; 87: 1123-32.
    CrossrefPubMedSearch in Google Scholar
  • 15 Cai L, Li W, Wang G. et al. Hyperglycemiainduced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway. Diabetes 2002; 51: 1938-48.
    CrossrefPubMedSearch in Google Scholar
  • 16 Ravanat C, Freund M, Mangin P. et al. GPV is a marker of in vivo platelet activation—study in a rat thrombosis model. Thromb Haemost 2000; 83: 327-33.
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Slupsky JR, 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: 1008-14.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Varo N, de Lemos JA, Libby P. et al. Soluble CD40L: risk prediction after acute coronary syndromes. Circulation 2003; 108: 1049-52.
    CrossrefPubMedSearch in Google Scholar
  • 19 Jacobson SH, Egberg N, Hylander B. et al. Correlation between soluble markers of endothelial dysfunction in patients with renal failure. Am J Nephrol 2002; 22: 42-7.
    CrossrefPubMedSearch in Google Scholar
  • 20 Gawaz M, Neumann FJ, Ott I. et al. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-37.
    CrossrefPubMedSearch in Google Scholar
  • 21 Ardissino D, Merlini PA, Bauer KA. et al. Thrombogenic potential of human coronary atherosclerotic plaques. Blood 2001; 98: 2726-9.
    CrossrefPubMedSearch in Google Scholar
  • 22 Mallat Z, Hugel B, Ohan J. et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-53.
    CrossrefPubMedSearch in Google Scholar
  • 23 Hugel B, Socie G, Vu T. et al. Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 1999; 93: 3451-6.
    PubMedSearch in Google Scholar
  • 24 Rossig L, Hoffmann J, Hugel B. et al. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation 2001; 104: 2182-7.
    CrossrefPubMedSearch in Google Scholar
  • 25 Azorsa DO, Moog S, Ravanat C. et al. Measurement of GPV released by activated platelets using a sensitive immunocapture ELISA—its use to follow platelet storage in transfusion. Thromb Haemost 1999; 81: 131-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Vidal C, Spaulding C, Picard F. et al. Flow cytometry detection of platelet procoagulation activity and microparticles in patients with unstable angina treated by percutaneous coronary angioplasty and stent implantation. Thromb Haemost 2001; 86: 784-90.
    Thieme ConnectPubMedSearch in Google Scholar
  • 27 Aoki I, Shimoyama K, Aoki N. et al. Plateletdependent thrombin generation in patients with diabetes mellitus: effects of glycemic control on coagulability in diabetes. J Am Coll Cardiol 1996; 27: 560-6.
    CrossrefPubMedSearch in Google Scholar
  • 28 van der Planken MG, Vertessen FJ, Vertommen J. et al. Platelet prothrombinase activity, a final pathway platelet procoagulant activity, is overexpressed in type 1 diabetes: no relationship with mean platelet volume or background retinopathy. Clin Appl Thromb Hemost 2000; 06: 65-8.
    CrossrefPubMedSearch in Google Scholar
  • 29 Nakano M, Furutani M, Shinno H. et al. Elevation of soluble thrombomodulin antigen levels in the serum and urine of streptozotocin-induced diabetes model rats. Thromb Res 2000; 99: 83-91.
    CrossrefPubMedSearch in Google Scholar
  • 30 Ouvina SM, La Greca RD, Zanaro NL. et al. Endothelial dysfunction, nitric oxide and platelet activation in hypertensive and diabetic type II patients. Thromb Res 2001; 102: 107-14.
    CrossrefPubMedSearch in Google Scholar
  • 31 Min C, Kang E, Yu SH. et al. Advanced glycation end products induce apoptosis and procoagulant activity in cultured human umbilical vein endothelial cells. Diabetes Res Clin Pract 1999; 46: 197-202.
    CrossrefPubMedSearch in Google Scholar
  • 32 Matsunaga T, Iguchi K, Nakajima T. et al. Glycated high-density lipoprotein induces apoptosis of endothelial cells via a mitochondrial dysfunction. Biochem Biophys Res Commun 2001; 287: 714-20.
    CrossrefPubMedSearch in Google Scholar
  • 33 Claise C, Edeas M, Chaouchi N. et al. Oxidized-LDL induce apoptosis in HUVEC but not in the endothelial cell line EA.hy 926. Atherosclerosis 1999; 147: 95-104.
    CrossrefPubMedSearch in Google Scholar
  • 34 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-52.
    CrossrefPubMedSearch in Google Scholar
  • 35 Barry OP, Pratico D, Lawson JA, FitzGerald GA. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest 1997; 99: 2118-27.
    CrossrefPubMedSearch in Google Scholar
  • 36 Nomura S, Tandon NN, Nakamura T. et al. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 2001; 158: 277-87.
    CrossrefPubMedSearch in Google Scholar
  • 37 Huber J, Vales A, Mitulovic G. et al. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler Thromb Vasc Biol 2002; 22: 101-7.
    CrossrefPubMedSearch in Google Scholar
  • 38 Nomura S, Imamura A, Okuno M. et al. Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines. Thromb Res 2000; 98: 257-68.
    CrossrefPubMedSearch in Google Scholar
  • 39 Merten M, Pakala R, Thiagarajan P. et al. Platelet microparticles promote platelet interaction with subendothelial matrix in a glycoprotein IIb/IIIa-dependent mechanism. Circulation 1999; 99: 2577-82.
    CrossrefPubMedSearch in Google Scholar
  • 40 Nomura S, Shouzu A, Omoto S. et al. Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes. Thromb Haemost 1998; 80: 388-92.
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Morel O, Jesel L, Hugel B. et al. Protective effects of Vitamin C on endothelium damage and platelet activation during myocardial infarction in patients with sustained generation of circulating microparticles. J Thromb Haemost 2003; 01: 171-7.
    CrossrefPubMedSearch in Google Scholar
  • 42 Blann AD, Lanza F, Galajda P. et al. Increased platelet glycoprotein V levels in patients with coronary and peripheral atherosclerosis—the influence of aspirin and cigarette smoking. Thromb Haemost 2001; 86: 777-83.
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Sabatier V, Roux V, Anfosso F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factordependent procoagulant activity. Blood 2002; 99: 3962-70.
    CrossrefPubMedSearch in Google Scholar
  • 44 Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999; 274: 23111-8.
    CrossrefPubMedSearch in Google Scholar
  • 45 Muller I, Klocke A, Alex M. et al. Intravascular tissue factors initiates coagulation via circulating microvesicles and platelets. FASEB J 2003; 17: 476-8.
    CrossrefPubMedSearch in Google Scholar