PDF herunterladen
Semin Thromb Hemost 2013; 39(05): 477-488
DOI: 10.1055/s-0033-1343888
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prothrombotic Changes in Diabetes Mellitus

Olivier Morel
1   Unité de recherche EA 7293 Stress vasculaire et tissulaire en Transplantation, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
2   Pôle d'activité médico-chirurgicale, Cardio-Vasculaire des Hôpitaux, Universitaires de Strasbourg, Strasbourg, France
,
Laurence Jesel
1   Unité de recherche EA 7293 Stress vasculaire et tissulaire en Transplantation, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
2   Pôle d'activité médico-chirurgicale, Cardio-Vasculaire des Hôpitaux, Universitaires de Strasbourg, Strasbourg, France
,
Malak Abbas
3   Plateforme de Recherche et d'Analyses en Sciences de l'Environnement, Ecole Doctorale des Sciences et Technologies, Université Libanaise, Hadath, Beirut, Lebanon, Beyruth, Lebanon
,
Nicolas Morel
4   Pôle d'Urgences, CHU Bordeaux, Bordeaux, France
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
29. April 2013 (online)

    Lizenzen und Reprints

Abstract

Although our understanding of vascular pathology has greatly improved in recent years, the cellular and molecular mechanisms underlying the enhanced thrombotic propensity in type 2 diabetes mellitus (T2DM) remain incompletely characterized. Detrimental interactions between activated vascular cells (i.e., platelets, leukocytes, endothelial cells) and the vulnerable atheromatous plaque are a major determinant of the increased atherothrombotic burden in T2DM patients. Endothelial damage and accelerated senescence, impairment of the endothelial progenitor cell repair system, plaque neovascularization and inflammation, decreased clearance of detrimental molecules within the plaque, and increased expression of matrix metalloproteinases may collectively contribute to intraplaque hemorrhage and subsequent rupture. Notably, recent data demonstrates the central importance of the tissue factor-microparticle–mediated pathway in diabetic thrombophilia and cardiovascular complications. Acting as detrimental amplifiers of various biological responses (including thrombogenicity and plaque remodeling), microparticles have also emerged as a key marker of global vascular damage in T2DM patients. Available evidence suggests that targeting the tissue factor-microparticle pathway may be a promising approach for reducing the burden of the atherosclerotic complications of diabetes.

Keywords

thrombosis - microparticles - tissue factor - myocardial infarction - platelet stimulation - endothelial damage - leukocyte activation - angiogenesis
 

  • References

  • 1 Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339 (4) 229-234
    CrossrefPubMedGoogle Scholar
  • 2 Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation 2010; 121 (17) 1896-1903
    CrossrefPubMedGoogle Scholar
  • 3 Wattanakit K, Lutsey PL, Bell EJ , et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost 2012; 108 (3) 508-515
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 4 Vazzana N, Ranalli P, Cuccurullo C, Davì G. Diabetes mellitus and thrombosis. Thromb Res 2012; 129 (3) 371-377
    CrossrefPubMedGoogle Scholar
  • 5 Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009; 53 (5, Suppl): S35-S42
    CrossrefPubMedGoogle Scholar
  • 6 Morel O, Kessler L, Ohlmann P, Bareiss P. Diabetes and the platelet: toward new therapeutic paradigms for diabetic atherothrombosis. Atherosclerosis 2010; 212 (2) 367-376
    CrossrefPubMedGoogle Scholar
  • 7 Tschoepe D, Roesen P, Esser J , et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991; 17 (4) 433-438
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 8 Guthikonda S, Alviar CL, Vaduganathan M , et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. J Am Coll Cardiol 2008; 52 (9) 743-749
    CrossrefPubMedGoogle Scholar
  • 9 Morel O, Hugel B, Jesel L , et al. Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus. Thromb Haemost 2004; 91 (2) 345-353
    PubMedGoogle Scholar
  • 10 Kakouros N, Rade JJ, Kourliouros A, Resar JR. Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective. Int J Endocrinol 2011; 2011: 742719
    PubMedGoogle Scholar
  • 11 Hernández Vera R, Vilahur G, Ferrer-Lorente R, Peña E, Badimon L. Platelets derived from the bone marrow of diabetic animals show dysregulated endoplasmic reticulum stress proteins that contribute to increased thrombosis. Arterioscler Thromb Vasc Biol 2012; 32 (9) 2141-2148
    CrossrefPubMedGoogle Scholar
  • 12 Santilli F, Formoso G, Sbraccia P , et al. Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus. J Thromb Haemost 2010; 8 (4) 828-837
    CrossrefPubMedGoogle Scholar
  • 13 Yngen M, Ostenson CG, Li N, Hjemdahl P, Wallén NH. Acute hyperglycemia increases soluble P-selectin in male patients with mild diabetes mellitus. Blood Coagul Fibrinolysis 2001; 12 (2) 109-116
    CrossrefPubMedGoogle Scholar
  • 14 Vaidyula VR, Rao AK, Mozzoli M, Homko C, Cheung P, Boden G. Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. Diabetes 2006; 55 (1) 202-208
    CrossrefPubMedGoogle Scholar
  • 15 Randriamboavonjy V, Pistrosch F, Bölck B , et al. Platelet sarcoplasmic endoplasmic reticulum Ca2+-ATPase and mu-calpain activity are altered in type 2 diabetes mellitus and restored by rosiglitazone. Circulation 2008; 117 (1) 52-60
    CrossrefPubMedGoogle Scholar
  • 16 Morel O, Toti F, Jesel L, Freyssinet JM. Mechanisms of microparticle generation: on the trail of the mitochondrion!. Semin Thromb Hemost 2010; 36 (8) 833-844
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Morel O, Jesel L, Freyssinet JM, Toti F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 2011; 31 (1) 15-26
    CrossrefPubMedGoogle Scholar
  • 18 Assert R, Scherk G, Bumbure A, Pirags V, Schatz H, Pfeiffer AF. Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro. Diabetologia 2001; 44 (2) 188-195
    CrossrefPubMedGoogle Scholar
  • 19 De Cristofaro R, Rocca B, Vitacolonna E , et al. Lipid and protein oxidation contribute to a prothrombotic state in patients with type 2 diabetes mellitus. J Thromb Haemost 2003; 1 (2) 250-256
    CrossrefPubMedGoogle Scholar
  • 20 Chappey O, Dosquet C, Wautier MP, Wautier JL. Advanced glycation end products, oxidant stress and vascular lesions. Eur J Clin Invest 1997; 27 (2) 97-108
    CrossrefPubMedGoogle Scholar
  • 21 Thomas G, Skrinska V, Lucas FV, Schumacher OP. Platelet glutathione and thromboxane synthesis in diabetes. Diabetes 1985; 34 (10) 951-954
    CrossrefPubMedGoogle Scholar
  • 22 Davì G, Catalano I, Averna M , et al. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 1990; 322 (25) 1769-1774
    CrossrefPubMedGoogle Scholar
  • 23 Queen LR, Ji Y, Goubareva I, Ferro A. Nitric oxide generation mediated by beta-adrenoceptors is impaired in platelets from patients with Type 2 diabetes mellitus. Diabetologia 2003; 46 (11) 1474-1482
    CrossrefPubMedGoogle Scholar
  • 24 Ferreira IA, Eybrechts KL, Mocking AI, Kroner C, Akkerman JW. IRS-1 mediates inhibition of Ca2+ mobilization by insulin via the inhibitory G-protein Gi. J Biol Chem 2004; 279 (5) 3254-3264
    PubMedGoogle Scholar
  • 25 Ferreira IA, Mocking AI, Feijge MA , et al. Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 2006; 26 (2) 417-422
    PubMedGoogle Scholar
  • 26 Falcon C, Pfliegler G, Deckmyn H, Vermylen J. The platelet insulin receptor: detection, partial characterization, and search for a function. Biochem Biophys Res Commun 1988; 157 (3) 1190-1196
    CrossrefPubMedGoogle Scholar
  • 27 Singla A, Antonino MJ, Bliden KP, Tantry US, Gurbel PA. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J 2009; 158 (5) e1-e6
    CrossrefPubMedGoogle Scholar
  • 28 Geisler T, Anders N, Paterok M , et al. Platelet response to clopidogrel is attenuated in diabetic patients undergoing coronary stent implantation. Diabetes Care 2007; 30 (2) 372-374
    CrossrefPubMedGoogle Scholar
  • 29 Vivas D, García-Rubira JC, Bernardo E , et al. Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study (“Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo”). Heart 2011; 97 (10) 803-809
    CrossrefPubMedGoogle Scholar
  • 30 Angiolillo DJ, Bernardo E, Ramírez C , et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol 2006; 48 (2) 298-304
    CrossrefPubMedGoogle Scholar
  • 31 Morel O, El Ghannudi S, Hess S , et al. The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: roles of white blood cell count and body weight. Thromb Haemost 2012; 108 (2) 338-348
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 32 Gaborit B, Frère C, Cuisset T, Alessi MC, Dutour A. Enhanced post-clopidogrel platelet reactivity in diabetic patients is independently related to plasma fibrinogen level but not to glycemic control. J Thromb Haemost 2009; 7 (11) 1939-1941
    CrossrefPubMedGoogle Scholar
  • 33 Mangiacapra F, Patti G, Peace A , et al. Comparison of platelet reactivity and periprocedural outcomes in patients with versus without diabetes mellitus and treated with clopidogrel and percutaneous coronary intervention. Am J Cardiol 2010; 106 (5) 619-623
    CrossrefPubMedGoogle Scholar
  • 34 Erlinge D, Varenhorst C, Braun OO , et al. Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 2008; 52 (24) 1968-1977
    CrossrefPubMedGoogle Scholar
  • 35 Geisler T, Mueller K, Aichele S , et al. Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol 2010; 99 (11) 743-752
    CrossrefPubMedGoogle Scholar
  • 36 Sanchez PL, Morinigo JL, Pabon P , et al. Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome. Heart 2004; 90 (3) 264-269
    CrossrefPubMedGoogle Scholar
  • 37 Vaidyula VR, Boden G, Rao AK. Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects. Platelets 2006; 17 (8) 577-585
    CrossrefPubMedGoogle Scholar
  • 38 Sage AT, Holtby-Ottenhof S, Shi Y, Damjanovic S, Sharma AM, Werstuck GH. Metabolic syndrome and acute hyperglycemia are associated with endoplasmic reticulum stress in human mononuclear cells. Obesity (Silver Spring) 2012; 20 (4) 748-755
    CrossrefPubMedGoogle Scholar
  • 39 Dasu MR, Devaraj S, Jialal I. High glucose induces IL-1beta expression in human monocytes: mechanistic insights. Am J Physiol Endocrinol Metab 2007; 293 (1) E337-E346
    CrossrefPubMedGoogle Scholar
  • 40 Venugopal SK, Devaraj S, Yang T, Jialal I. Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. Diabetes 2002; 51 (10) 3049-3054
    CrossrefPubMedGoogle Scholar
  • 41 Gawlowski T, Stratmann B, Stirban AO, Negrean M, Tschoepe D. AGEs and methylglyoxal induce apoptosis and expression of Mac-1 on neutrophils resulting in platelet-neutrophil aggregation. Thromb Res 2007; 121 (1) 117-126
    CrossrefPubMedGoogle Scholar
  • 42 Ling L, Shen Y, Wang K , et al. Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization. PLoS ONE 2012; 7 (11) e50739
    CrossrefPubMedGoogle Scholar
  • 43 Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol 2004; 44 (12) 2293-2300
    CrossrefPubMedGoogle Scholar
  • 44 Rubenstein DA, Maria Z, Yin W. Glycated albumin modulates endothelial cell thrombogenic and inflammatory responses. J Diabetes Sci Tech 2011; 5 (3) 703-713
    PubMedGoogle Scholar
  • 45 Otsuka A, Azuma K, Iesaki T , et al. Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta. Diabetologia 2005; 48 (12) 2667-2674
    CrossrefPubMedGoogle Scholar
  • 46 Vogl-Willis CA, Edwards IJ. High glucose-induced alterations in subendothelial matrix perlecan leads to increased monocyte binding. Arterioscler Thromb Vasc Biol 2004; 24 (5) 858-863
    CrossrefPubMedGoogle Scholar
  • 47 Moreno PR, Murcia AM, Palacios IF , et al. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation 2000; 102 (18) 2180-2184
    CrossrefPubMedGoogle Scholar
  • 48 Burke AP, Kolodgie FD, Zieske A , et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol 2004; 24 (7) 1266-1271
    CrossrefPubMedGoogle Scholar
  • 49 Tabas I, Seimon T, Arellano J , et al. The impact of insulin resistance on macrophage death pathways in advanced atherosclerosis. Novartis Found Symp 2007; 286: 99-109 , discussion 109–112, 162–163, 196–203
    PubMedGoogle Scholar
  • 50 Purushothaman KR, Purushothaman M, Muntner P , et al. Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: implication for plaque progression in diabetic atherosclerosis. Vasc Med 2011; 16 (2) 103-108
    CrossrefPubMedGoogle Scholar
  • 51 Pandolfi A, De Filippis EA. Chronic hyperglycemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications. Genes Nutr 2007; 2 (2) 195-208
    CrossrefPubMedGoogle Scholar
  • 52 Olson FJ, Strömberg S, Hjelmgren O, Kjelldahl J, Fagerberg B, Bergström GM. Increased vascularization of shoulder regions of carotid atherosclerotic plaques from patients with diabetes. J Vasc Surg 2011; 54 (5) 1324-1331 , e5
    CrossrefPubMedGoogle Scholar
  • 53 Moreno PR, Purushothaman M, Purushothaman KR. Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann N Y Acad Sci 2012; 1254: 7-17
    CrossrefPubMedGoogle Scholar
  • 54 Levy AP, Purushothaman KR, Levy NS , et al. Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage and plaque vulnerability. Circ Res 2007; 101 (1) 106-110
    CrossrefPubMedGoogle Scholar
  • 55 Osende JI, Badimon JJ, Fuster V , et al. Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control. J Am Coll Cardiol 2001; 38 (5) 1307-1312
    CrossrefPubMedGoogle Scholar
  • 56 Davì G, Gennaro F, Spatola A , et al. Thrombin-antithrombin III complexes in type II diabetes mellitus. J Diabetes Complications 1992; 6 (1) 7-11
    CrossrefPubMedGoogle Scholar
  • 57 Wasty F, Alavi MZ, Moore S. Distribution of glycosaminoglycans in the intima of human aortas: changes in atherosclerosis and diabetes mellitus. Diabetologia 1993; 36 (4) 316-322
    CrossrefPubMedGoogle Scholar
  • 58 Borcea V, Morcos M, Isermann B , et al. Influence of ramipril on the course of plasma thrombomodulin in patients with diabetes mellitus. Vasa 1999; 28 (3) 172-180
    CrossrefPubMedGoogle Scholar
  • 59 Fujiwara Y, Tagami S, Kawakami Y. Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy. J Atheroscler Thromb 1998; 5 (1) 21-28
    PubMedGoogle Scholar
  • 60 Isermann B, Vinnikov IA, Madhusudhan T , et al. Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis. Nat Med 2007; 13 (11) 1349-1358
    CrossrefPubMedGoogle Scholar
  • 61 Hernestål-Boman J, Norberg M, Jansson JH , et al. Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study. Cardiovasc Diabetol 2012; 11: 152
    CrossrefPubMedGoogle Scholar
  • 62 Tripodi A, Branchi A, Chantarangkul V , et al. Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay. J Thromb Thrombolysis 2011; 31 (2) 165-172
    CrossrefPubMedGoogle Scholar
  • 63 Tsimerman G, Roguin A, Bachar A, Melamed E, Brenner B, Aharon A. Involvement of microparticles in diabetic vascular complications. Thromb Haemost 2011; 106 (2) 310-321
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 64 Jung KH, Chu K, Lee ST , et al. Risk of macrovascular complications in type 2 diabetes mellitus: endothelial microparticle profiles. Cerebrovasc Dis 2011; 31 (5) 485-493
    CrossrefPubMedGoogle Scholar
  • 65 Bogdanov VY, Osterud B. Cardiovascular complications of diabetes mellitus: the tissue factor perspective. Thromb Res 2010; 125 (2) 112-118
    CrossrefPubMedGoogle Scholar
  • 66 Ichikawa K, Yoshinari M, Iwase M , et al. Advanced glycosylation end products induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients. Atherosclerosis 1998; 136 (2) 281-287
    CrossrefPubMedGoogle Scholar
  • 67 Boden G, Vaidyula VR, Homko C, Cheung P, Rao AK. Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: effects of insulin and glucose. J Clin Endocrinol Metab 2007; 92 (11) 4352-4358
    CrossrefPubMedGoogle Scholar
  • 68 Morel O, Toti F, Hugel B , et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2594-2604
    CrossrefPubMedGoogle Scholar
  • 69 Morel O, Pereira B, Averous G , et al. Increased levels of procoagulant tissue factor-bearing microparticles within the occluded coronary artery of patients with ST-segment elevation myocardial infarction: role of endothelial damage and leukocyte activation. Atherosclerosis 2009; 204 (2) 636-641
    CrossrefPubMedGoogle Scholar
  • 70 Falati S, Liu Q, Gross P , et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197 (11) 1585-1598
    CrossrefPubMedGoogle Scholar
  • 71 Lacroix R, Dignat-George F. Microparticles: new protagonists in pericellular and intravascular proteolysis. Semin Thromb Hemost 2013; 39 (1) 33-39
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 72 Lozito TP, Tuan RS. Endothelial cell microparticles act as centers of matrix metalloproteinsase-2 (MMP-2) activation and vascular matrix remodeling. J Cell Physiol 2012; 227 (2) 534-549
    CrossrefPubMedGoogle Scholar
  • 73 Ettelaie C, Su S, Li C, Collier ME. Tissue factor-containing microparticles released from mesangial cells in response to high glucose and AGE induce tube formation in microvascular cells. Microvasc Res 2008; 76 (3) 152-160
    CrossrefPubMedGoogle Scholar
  • 74 Chahed S, Leroyer AS, Benzerroug M , et al. Increased vitreous shedding of microparticles in proliferative diabetic retinopathy stimulates endothelial proliferation. Diabetes 2010; 59 (3) 694-701
    CrossrefPubMedGoogle Scholar
  • 75 Steppich BA, Braun SL, Stein A , et al. Plasma TF activity predicts cardiovascular mortality in patients with acute myocardial infarction. Thromb J 2009; 7: 11
    CrossrefPubMedGoogle Scholar
  • 76 Porto I, Biasucci LM, De Maria GL , et al. Intracoronary microparticles and microvascular obstruction in patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. Eur Heart J 2012; 33 (23) 2928-2938
    CrossrefPubMedGoogle Scholar
  • 77 Sinning JM, Losch J, Walenta K, Böhm M, Nickenig G, Werner N. Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 2011; 32 (16) 2034-2041
    CrossrefPubMedGoogle Scholar
  • 78 Nozaki T, Sugiyama S, Koga H , et al. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol 2009; 54 (7) 601-608
    CrossrefPubMedGoogle Scholar
  • 79 Chen J, Chen S, Chen Y , et al. Circulating endothelial progenitor cells and cellular membrane microparticles in db/db diabetic mouse: possible implications in cerebral ischemic damage. Am J Physiol Endocrinol Metab 2011; 301 (1) E62-E71
    CrossrefPubMedGoogle Scholar
  • 80 Curtis AM, Zhang L, Medenilla E , et al. Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population. Cytometry B Clin Cytom 2010; 78 (5) 329-337
    PubMedGoogle Scholar
  • 81 Chen Y, Feng B, Li X, Ni Y, Luo Y. Plasma endothelial microparticles and their correlation with the presence of hypertension and arterial stiffness in patients with type 2 diabetes. J Clin Hypertens (Greenwich) 2012; 14 (7) 455-460
    CrossrefPubMedGoogle Scholar
  • 82 Pirro M, Schillaci G, Bagaglia F , et al. Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk. Atherosclerosis 2008; 197 (2) 757-767
    CrossrefPubMedGoogle Scholar
  • 83 Feng B, Chen Y, Luo Y, Chen M, Li X, Ni Y. Circulating level of microparticles and their correlation with arterial elasticity and endothelium-dependent dilation in patients with type 2 diabetes mellitus. Atherosclerosis 2010; 208 (1) 264-269
    CrossrefPubMedGoogle Scholar
  • 84 Koga H, Sugiyama S, Kugiyama K , et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2005; 45 (10) 1622-1630
    CrossrefPubMedGoogle Scholar
  • 85 Huang PH, Huang SS, Chen YH , et al. Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. J Hypertens 2010; 28 (8) 1655-1665
    CrossrefPubMedGoogle Scholar
  • 86 Wiviott SD, Braunwald E, Angiolillo DJ , et al; TRITON-TIMI 38 Investigators. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation 2008; 118 (16) 1626-1636
    CrossrefPubMedGoogle Scholar
  • 87 James S, Angiolillo DJ, Cornel JH , et al; PLATO Study Group. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2010; 31 (24) 3006-3016
    CrossrefPubMedGoogle Scholar
  • 88 Wang TH, Bhatt DL, Fox KA , et al; CHARISMA Investigators. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur Heart J 2007; 28 (18) 2200-2207
    CrossrefPubMedGoogle Scholar
  • 89 Gerrits AJ, Koekman CA, Yildirim C, Nieuwland R, Akkerman JW. Insulin inhibits tissue factor expression in monocytes. J Thromb Haemost 2009; 7 (1) 198-205
    CrossrefPubMedGoogle Scholar
  • 90 Henriksson CE, Hellum M, Haug KB , et al. Anticoagulant effects of an antidiabetic drug on monocytes in vitro. Thromb Res 2011; 128 (5) e100-e106
    CrossrefPubMedGoogle Scholar
  • 91 Nomura S, Omoto S, Yokoi T , et al. Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus. Int J Gen Med 2011; 4: 539-545
    PubMedGoogle Scholar
  • 92 Esposito K, Maiorino MI, Di Palo C , et al. Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes—a randomized controlled trial. Diabetes Obes Metab 2011; 13 (5) 439-445
    CrossrefPubMedGoogle Scholar
  • 93 Tramontano AF, O'Leary J, Black AD, Muniyappa R, Cutaia MV, El-Sherif N. Statin decreases endothelial microparticle release from human coronary artery endothelial cells: implication for the Rho-kinase pathway. Biochem Biophys Res Commun 2004; 320 (1) 34-38
    CrossrefPubMedGoogle Scholar
  • 94 Sommeijer DW, Joop K, Leyte A, Reitsma PH, ten Cate H. Pravastatin reduces fibrinogen receptor gpIIIa on platelet-derived microparticles in patients with type 2 diabetes. J Thromb Haemost 2005; 3 (6) 1168-1171
    CrossrefPubMedGoogle Scholar
  • 95 Tehrani S, Mobarrez F, Antovic A , et al. Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia. Thromb Res 2010; 126 (3) e225-e231
    CrossrefPubMedGoogle Scholar
  • 96 Nomura S, Inami N, Shouzu A , et al. The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients. Platelets 2009; 20 (1) 16-22
    CrossrefPubMedGoogle Scholar
  • 97 Koh KK, Quon MJ, Han SH, Ahn JY, Lee Y, Shin EK. Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. Atherosclerosis 2007; 194 (1) 230-237
    CrossrefPubMedGoogle Scholar
  • 98 Diamant M, Tushuizen ME, Abid-Hussein MN , et al. Simvastatin-induced endothelial cell detachment and microparticle release are prenylation dependent. Thromb Haemost 2008; 100 (3) 489-497
    PubMedGoogle Scholar
  • 99 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; 1 (1) 171-177
    CrossrefPubMedGoogle Scholar
  • 100 Nomura S, Shouzu A, Omoto S , et al. Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J Atheroscler Thromb 2009; 16 (2) 83-90
    CrossrefPubMedGoogle Scholar
  • 101 Morel O, Luca F, Grunebaum L , et al. Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles. Int J Obes (Lond) 2011; 35 (12) 1479-1486
    CrossrefPubMedGoogle Scholar
  • 102 Cheng V, Kashyap SR, Schauer PR, Kirwan JP, McCrae KR. Restoration of glycemic control in patients with type 2 diabetes mellitus after bariatric surgery is associated with reduction in microparticles. Surg Obes Relat Dis 2011;
    PubMedGoogle Scholar
  • 103 Shimazu T, Inami N, Satoh D , et al. Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients. J Thromb Thrombolysis 2009; 28 (4) 429-435
    CrossrefPubMedGoogle Scholar