Semin Thromb Hemost 2022; 48(02): 188-205
DOI: 10.1055/s-0041-1740150
Review Article

Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting

Siphosethu Cassandra Maphumulo
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
,
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
› Author Affiliations

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

Authors' Contributions

S.M. has written the paper; E.P. has edited the paper, and is study leader and co-corresponding author.




Publication History

Article published online:
27 December 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Pheiffer C, Pillay-van Wyk V, Joubert JD, Levitt N, Nglazi MD, Bradshaw D. The prevalence of type 2 diabetes in South Africa: a systematic review protocol. BMJ Open 2018; 8 (07) e021029
  • 2 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (Suppl. 01) S62-S69
  • 3 Tsalamandris S, Antonopoulos AS, Oikonomou E. et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol 2019; 14 (01) 50-59
  • 4 WHO. Diabetes. Fact sheet N 312. 2011 . Available at: http://www.who.int/mediacentre/factsheets/fs312/en/index.html
  • 5 Phasha MN, Soma P, Pretorius E, Phulukdaree A. Coagulopathy in type 2 diabetes mellitus: pathological mechanisms and the role of factor XIII-A single nucleotide polymorphisms. Curr Diabetes Rev 2019; 15 (06) 446-455
  • 6 Galicia-Garcia U, Benito-Vicente A, Jebari S. et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci 2020; 21 (17) 6275
  • 7 Diabetes Atlas IDF. 9th ed. Accessed November 8, 2021 at: https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html
  • 8 Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes 2015; 6 (13) 1246-1258
  • 9 Asmelash D, Asmelash Y. The burden of undiagnosed diabetes mellitus in adult African population: a systematic review and meta-analysis. J Diabetes Res 2019; 2019: 4134937
  • 10 Reddy PH. Can diabetes be controlled by lifestyle activities?. Curr Res Diabetes Obes J 2017; 1 (04) 555568
  • 11 Peer N, Kengne AP, Motala AA, Mbanya JC. Diabetes in the Africa Region: an update. Diabetes Res Clin Pract 2014; 103 (02) 197-205
  • 12 Mayosi BM. The 10 ‘Best Buys’ to combat heart disease, diabetes and stroke in Africa. Heart 2013; 99 (14) 973-974
  • 13 Mahler RJ, Adler ML. Clinical review 102: type 2 diabetes mellitus: update on diagnosis, pathophysiology, and treatment. J Clin Endocrinol Metab 1999; 84 (04) 1165-1171
  • 14 Chang-Chen KJ, Mullur R, Bernal-Mizrachi E. Beta-cell failure as a complication of diabetes. Rev Endocr Metab Disord 2008; 9 (04) 329-343
  • 15 Ashcroft FM, Rorsman P. Diabetes mellitus and the β cell: the last ten years. Cell 2012; 148 (06) 1160-1171
  • 16 Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp Mol Med 2016; 48: e219
  • 17 Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011; 11 (02) 98-107
  • 18 Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne) 2013; 4: 37
  • 19 Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 2018; 14 (02) 88-98
  • 20 Randeria SN, Thomson GJA, Nell TA, Roberts T, Pretorius E. Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation. Cardiovasc Diabetol 2019; 18 (01) 72
  • 21 Pretorius E. Platelets as potent signaling entities in type 2 diabetes mellitus. Trends Endocrinol Metab 2019; 30 (08) 532-545
  • 22 Bajpai A, Tilley DG. The role of leukocytes in diabetic cardiomyopathy. Front Physiol 2018; 9: 1547
  • 23 Chen L, Deng H, Cui H. et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2017; 9 (06) 7204-7218
  • 24 Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care 2011; 34 (Suppl. 02) S285-S290
  • 25 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 (08) 841-843
  • 26 Sabatier F, Darmon P, Hugel B. et al. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes 2002; 51 (09) 2840-2845
  • 27 Simak J, Gelderman MP, Yu H, Wright V, Baird AE. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J Thromb Haemost 2006; 4 (06) 1296-1302
  • 28 Preston RA, Jy W, Jimenez JJ. et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension 2003; 41 (02) 211-217
  • 29 Meziani F, Tesse A, Andriantsitohaina R. Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases. Pharmacol Rep 2008; 60 (01) 75-84
  • 30 Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Żuber Z, Wojtkiewicz M, Wojtkiewicz J. Role of microparticles in the pathogenesis of inflammatory joint diseases. Int J Mol Sci 2019; 20 (21) E5453
  • 31 Simak J, Gelderman MP. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev 2006; 20 (01) 1-26
  • 32 Freeman DW, Noren Hooten N, Eitan E. et al. Altered extracellular vesicle concentration, cargo, and function in diabetes. Diabetes 2018; 67 (11) 2377-2388
  • 33 Chen J, Chung DW. Inflammation, von Willebrand factor, and ADAMTS13. Blood 2018; 132 (02) 141-147
  • 34 Distler JH, Huber LC, Hueber AJ. et al. The release of microparticles by apoptotic cells and their effects on macrophages. Apoptosis 2005; 10 (04) 731-741
  • 35 Puddu P, Puddu GM, Cravero E, Muscari S, Muscari A. The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases. Can J Cardiol 2010; 26 (04) 140-145
  • 36 Stevenson EV, Alexander JS, Yun JW. et al. Mechanisms of blood–brain barrier disintegration in the pathophysiology of multiple sclerosis. Mult Scler 2016; 393-413
  • 37 Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2 (08) 569-579
  • 38 Caruso S, Poon IKH. Apoptotic cell-derived extracellular vesicles: more than just debris. Front Immunol 2018; 9: 1486
  • 39 VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59 (02) 277-287
  • 40 Schindler SM, Little JP, Klegeris A. Microparticles: a new perspective in central nervous system disorders. BioMed Res Int 2014; 2014: 756327
  • 41 Albert V, Subramanian A, Pati HP. Correlation of circulating microparticles with coagulation and fibrinolysis is healthy individuals. Blood 2018; 132 (Suppl. 01) 4975-4975
  • 42 Cauwenberghs S, Feijge MA, Harper AG, Sage SO, Curvers J, Heemskerk JW. Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton. FEBS Lett 2006; 580 (22) 5313-5320
  • 43 Chen Y, Li G, Liu ML. Microvesicles as emerging biomarkers and therapeutic targets in cardiometabolic diseases. Genomics Proteomics Bioinformatics 2018; 16 (01) 50-62
  • 44 Reid VL, Webster NR. Role of microparticles in sepsis. Br J Anaesth 2012; 109 (04) 503-513
  • 45 Shantsila E, Kamphuisen PW, Lip GY. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis. J Thromb Haemost 2010; 8 (11) 2358-2368
  • 46 Morel O, Toti F, Bakouboula B, Grunebaum L, Freyssinet JM. Procoagulant microparticles: ‘criminal partners’ in atherothrombosis and deleterious cellular exchanges. Pathophysiol Haemost Thromb 2006; 35 (1-2): 15-22
  • 47 Leopold JA. The endothelium. In: Vascular Medicine: A Companion to Braunwald's Heart Disease. Philadelphia, PA: Elsevier; 2013: 14-24 :chap 2.
  • 48 Li S, Wei J, Zhang C. et al. Cell-derived microparticles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Cell Physiol Biochem 2016; 39 (06) 2439-2450
  • 49 Santilli F, Marchisio M, Lanuti P, Boccatonda A, Miscia S, Davì G. Microparticles as new markers of cardiovascular risk in diabetes and beyond. Thromb Haemost 2016; 116 (02) 220-234
  • 50 Tramontano AF, Lyubarova R, Tsiakos J, Palaia T, Deleon JR, Ragolia L. Circulating endothelial microparticles in diabetes mellitus. Mediators Inflamm 2010; 2010: 250476
  • 51 Zhang X, McGeoch SC, Johnstone AM. et al. Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status. J Thromb Thrombolysis 2014; 37 (04) 455-463
  • 52 Davì G, Ferroni P. Microparticles in type 2 diabetes mellitus. J Thromb Haemost 2005; 3 (06) 1166-1167
  • 53 Nomura S. Dynamic role of microparticles in type 2 diabetes mellitus. Curr Diabetes Rev 2009; 5 (04) 245-251
  • 54 Gkaliagkousi E, Nikolaidou B, Gavriilaki E. et al. Increased erythrocyte- and platelet-derived microvesicles in newly diagnosed type 2 diabetes mellitus. Diab Vasc Dis Res 2019; 16 (05) 458-465
  • 55 Ferroni P, Basili S, Falco A, Davì G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2004; 2 (08) 1282-1291
  • 56 Leroyer AS, Isobe H, Lesèche G. et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 2007; 49 (07) 772-777
  • 57 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
  • 58 Zaldivia MTK, McFadyen JD, Lim B, Wang X, Peter K. Platelet-derived microvesicles in cardiovascular diseases. Front Cardiovasc Med 2017; 4: 74
  • 59 Tushuizen ME, Nieuwland R, Rustemeijer C. et al. Elevated endothelial microparticles following consecutive meals are associated with vascular endothelial dysfunction in type 2 diabetes. Diabetes Care 2007; 30 (03) 728-730
  • 60 Amabile N, Heiss C, Real WM. et al. Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension. Am J Respir Crit Care Med 2008; 177 (11) 1268-1275
  • 61 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
  • 62 Mackman N, Davis GE. Blood coagulation and blood vessel development: is tissue factor the missing link?. Arterioscler Thromb Vasc Biol 2011; 31 (11) 2364-2366
  • 63 Li KY, Zheng L, Wang Q, Hu YW. Characteristics of erythrocyte-derived microvesicles and its relation with atherosclerosis. Atherosclerosis 2016; 255: 140-144
  • 64 Keymel S, Heiss C, Kleinbongard P, Kelm M, Lauer T. Impaired red blood cell deformability in patients with coronary artery disease and diabetes mellitus. Horm Metab Res 2011; 43 (11) 760-765
  • 65 Angelillo-Scherrer A. Leukocyte-derived microparticles in vascular homeostasis. Circ Res 2012; 110 (02) 356-369
  • 66 Omoto S, Nomura S, Shouzu A, Nishikawa M, Fukuhara S, Iwasaka T. Detection of monocyte-derived microparticles in patients with type II diabetes mellitus. Diabetologia 2002; 45 (04) 550-555
  • 67 Berezin AE, Kremzer AA, Cammarota G. et al. Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure. Clin Chem Lab Med 2016; 54 (07) 1259-1267
  • 68 Zhang Y, Shi L, Mei H. et al. Inflamed macrophage microvesicles induce insulin resistance in human adipocytes. Nutr Metab (Lond) 2015; 12: 21
  • 69 Deng F, Wang S, Zhang L. Endothelial microparticles act as novel diagnostic and therapeutic biomarkers of diabetes and its complications: a literature review. BioMed Res Int 2016; 2016: 9802026
  • 70 Ogata N, Nomura S, Shouzu A, Imaizumi M, Arichi M, Matsumura M. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy. Diabetes Res Clin Pract 2006; 73 (03) 241-248
  • 71 Benameur T, Osman A, Parray A, Ait Hssain A, Munusamy S, Agouni A. Molecular mechanisms underpinning microparticle-mediated cellular injury in cardiovascular complications associated with diabetes. Oxid Med Cell Longev 2019; 2019: 6475187
  • 72 Xiao Y, Zheng L, Zou X, Wang J, Zhong J, Zhong T. Extracellular vesicles in type 2 diabetes mellitus: key roles in pathogenesis, complications, and therapy. J Extracell Vesicles 2019; 8 (01) 1625677
  • 73 Rodrigues KF, Pietrani NT, Fernandes AP. et al. Circulating microparticles levels are increased in patients with diabetic kidney disease: a case-control research. Clin Chim Acta 2018; 479: 48-55
  • 74 Lu CC, Ma KL, Ruan XZ, Liu BC. The emerging roles of microparticles in diabetic nephropathy. Int J Biol Sci 2017; 13 (09) 1118-1125
  • 75 Burger D, Thibodeau JF, Holterman CE, Burns KD, Touyz RM, Kennedy CR. Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury. J Am Soc Nephrol 2014; 25 (07) 1401-1407
  • 76 Ogata N, Imaizumi M, Nomura S. et al. Increased levels of platelet-derived microparticles in patients with diabetic retinopathy. Diabetes Res Clin Pract 2005; 68 (03) 193-201
  • 77 Su Y, Chen J, Dong Z. et al. Procoagulant activity of blood and endothelial cells via phosphatidylserine exposure and microparticle delivery in patients with diabetic retinopathy. Cell Physiol Biochem 2018; 45 (06) 2411-2420
  • 78 Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med 2013; 11: 117
  • 79 Tushuizen ME, Diamant M, Sturk A, Nieuwland R. Cell-derived microparticles in the pathogenesis of cardiovascular disease: friend or foe?. Arterioscler Thromb Vasc Biol 2011; 31 (01) 4-9
  • 80 Biasucci LM, Porto I, Di Vito L. et al. Differences in microparticle release in patients with acute coronary syndrome and stable angina. Circ J 2012; 76 (09) 2174-2182
  • 81 Bernard S, Loffroy R, Sérusclat A. et al. Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in type 2 diabetic patients with coronary noncalcified plaques evaluated by multidetector computed tomography (MDCT). Atherosclerosis 2009; 203 (02) 429-435
  • 82 Bernal-Mizrachi L, Jy W, Jimenez JJ. et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J 2003; 145 (06) 962-970
  • 83 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 (07) 455-460
  • 84 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 (01) 264-269
  • 85 Luo B, Huang F, Liu Y. et al. NLRP3 inflammasome as a molecular marker in diabetic cardiomyopathy. Front Physiol 2017; 8: 519
  • 86 Zhou W, Chen C, Chen Z. et al. NLRP3: a novel mediator in cardiovascular disease. J Immunol Res 2018; 2018: 5702103
  • 87 Rogers LC, Frykberg RG, Armstrong DG. et al. The Charcot foot in diabetes. Diabetes Care 2011; 34 (09) 2123-2129
  • 88 Nóbrega MB, Aras R, Netto EM. et al. Risk factors for Charcot foot. Arch Endocrinol Metab 2015; 59 (03) 226-230
  • 89 Pasquier J, Thomas B, Hoarau-Véchot J. et al. Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction. Sci Rep 2017; 7 (01) 16450
  • 90 Armstrong DG, Lavery LA. Diabetic foot ulcers: prevention, diagnosis and classification. Am Fam Physician 1998; 57 (06) 1325-1332 , 1337–1338
  • 91 Tsimerman G, Roguin A, Bachar A, Melamed E, Brenner B, Aharon A. Involvement of microparticles in diabetic vascular complications. Thromb Haemost 2011; 106 (02) 310-321
  • 92 Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13 (03) 269-288
  • 93 George FD. Microparticles in vascular diseases. Thromb Res 2008; 122 (Suppl. 01) S55-S59
  • 94 Voukalis C, Shantsila E, Lip GYH. Microparticles and cardiovascular diseases. Ann Med 2019; 51 (3-4): 193-223
  • 95 Hugel B, Martínez MC, Kunzelmann C, Freyssinet JM. Membrane microparticles: two sides of the coin. Physiology (Bethesda) 2005; 20: 22-27
  • 96 Hill CN, Hernández-Cáceres MP, Asencio C, Torres B, Solis B, Owen GI. Deciphering the role of the coagulation cascade and autophagy in cancer-related thrombosis and metastasis. Front Oncol 2020; 10: 605314
  • 97 Qu M, Zou X, Fang F. et al. Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p. Nat Commun 2020; 11 (01) 4964
  • 98 Holy EW, Tanner FC. Tissue factor in cardiovascular disease pathophysiology and pharmacological intervention. Adv Pharmacol 2010; 59: 259-292
  • 99 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
  • 100 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
  • 101 Diamant M, Nieuwland R, Pablo RF, Sturk A, Smit JW, Radder JK. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002; 106 (19) 2442-2447
  • 102 Ueba T, Haze T, Sugiyama M. et al. Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome. Thromb Haemost 2008; 100 (02) 280-285
  • 103 Viles-Gonzalez JF, Fuster V, Badimon JJ. Links between inflammation and thrombogenicity in atherosclerosis. Curr Mol Med 2006; 6 (05) 489-499
  • 104 Biró E, Sturk-Maquelin KN, Vogel GM. et al. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 2003; 1 (12) 2561-2568
  • 105 Westerman M, Porter JB. Red blood cell-derived microparticles: an overview. Blood Cells Mol Dis 2016; 59: 134-139
  • 106 Rubin O, Delobel J, Prudent M. et al. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation. Transfusion 2013; 53 (08) 1744-1754
  • 107 Van Der Meijden PE, Van Schilfgaarde M, Van Oerle R, Renné T, ten Cate H, Spronk HM. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 2012; 10 (07) 1355-1362
  • 108 Sinauridze EI, Kireev DA, Popenko NY. et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost 2007; 97 (03) 425-434
  • 109 Hoffman M, Monroe DM, Roberts HR. Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study. Thromb Haemost 1992; 68 (01) 74-78
  • 110 Hamilton KK, Hattori R, Esmon CT, Sims PJ. Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 1990; 265 (07) 3809-3814
  • 111 Jy W, Jimenez JJ, Mauro LM. et al. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost 2005; 3 (06) 1301-1308
  • 112 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
  • 113 Litvinov RI, Faizullin DA, Zuev YF, Weisel JW. The α-helix to β-sheet transition in stretched and compressed hydrated fibrin clots. Biophys J 2012; 103 (05) 1020-1027
  • 114 Kattula S, Byrnes JR, Wolberg AS. Fibrinogen and fibrin in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 2017; 37 (03) e13-e21
  • 115 Zubairova LD, Nabiullina RM, Nagaswami C. et al. Circulating microparticles alter formation, structure, and properties of fibrin clots. Sci Rep 2015; 5: 17611
  • 116 Campbell RA, Overmyer KA, Bagnell CR, Wolberg AS. Cellular procoagulant activity dictates clot structure and stability as a function of distance from the cell surface. Arterioscler Thromb Vasc Biol 2008; 28 (12) 2247-2254
  • 117 Campbell RA, Overmyer KA, Selzman CH, Sheridan BC, Wolberg AS. Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability. Blood 2009; 114 (23) 4886-4896
  • 118 Weisel JW, Litvinov RI. Mechanisms of fibrin polymerization and clinical implications. Blood 2013; 121 (10) 1712-1719
  • 119 Pretorius E, Mbotwe S, Kell DB. Lipopolysaccharide-binding protein (LBP) reverses the amyloid state of fibrin seen in plasma of type 2 diabetics with cardiovascular co-morbidities. Sci Rep 2017; 7 (01) 9680
  • 120 Pretorius L, Thomson GJA, Adams RCM, Nell TA, Laubscher WA, Pretorius E. Platelet activity and hypercoagulation in type 2 diabetes. Cardiovasc Diabetol 2018; 17 (01) 141
  • 121 Aleman MM, Gardiner C, Harrison P, Wolberg AS. Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability. J Thromb Haemost 2011; 9 (11) 2251-2261
  • 122 Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 1999; 94 (11) 3791-3799
  • 123 Litvinov RI, Shuman H, Bennett JS, Weisel JW. Binding strength and activation state of single fibrinogen-integrin pairs on living cells. Proc Natl Acad Sci U S A 2002; 99 (11) 7426-7431
  • 124 De Oliveira S, Vitorino de Almeida V, Calado A, Rosário HS, Saldanha C. Integrin-associated protein (CD47) is a putative mediator for soluble fibrinogen interaction with human red blood cells membrane. Biochim Biophys Acta 2012; 1818 (03) 481-490
  • 125 Carvalho FA, Connell S, Miltenberger-Miltenyi G. et al. Atomic force microscopy-based molecular recognition of a fibrinogen receptor on human erythrocytes. ACS Nano 2010; 4 (08) 4609-4620
  • 126 Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci (Lond) 2013; 124 (07) 423-441
  • 127 Daniel L, Fakhouri F, Joly D. et al. Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis. Kidney Int 2006; 69 (08) 1416-1423
  • 128 Fourcade O, Simon MF, Viodé C. et al. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 1995; 80 (06) 919-927
  • 129 Meziani F, Tesse A, David E. et al. Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility. Am J Pathol 2006; 169 (04) 1473-1483
  • 130 Akermann MR. Inflammation and Healing. In: Pathological Basis of Veterinary Disease: Expert Consult. St. Louis, MO: Mosby-Elsevier; 2017: 73-131.e2
  • 131 Wolf P, Nghiem DX, Walterscheid JP. et al. Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis. Am J Pathol 2006; 169 (03) 795-805
  • 132 Mesri M, Altieri DC. Endothelial cell activation by leukocyte microparticles. J Immunol 1998; 161 (08) 4382-4387
  • 133 Barry OP, Praticò D, Savani RC, FitzGerald GA. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998; 102 (01) 136-144
  • 134 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 (09) 2118-2127
  • 135 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 (01) 101-107
  • 136 Xie RF, Hu P, Wang ZC. et al. Platelet-derived microparticles induce polymorphonuclear leukocyte-mediated damage of human pulmonary microvascular endothelial cells. Transfusion 2015; 55 (05) 1051-1057
  • 137 Forlow SB, McEver RP, Nollert MU. Leukocyte-leukocyte interactions mediated by platelet microparticles under flow. Blood 2000; 95 (04) 1317-1323
  • 138 Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 2004; 43 (02) 428-433
  • 139 Barry OP, Kazanietz MG, Praticò D, FitzGerald GA. Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. J Biol Chem 1999; 274 (11) 7545-7556
  • 140 Štok U, Čučnik S, Sodin-Šemrl S, Žigon P. Extracellular vesicles and antiphospholipid syndrome: state-of-the-art and future challenges. Int J Mol Sci 2021; 22 (09) 4689
  • 141 Khan N, Farooq AD, Sadek B. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists. Drug Des Devel Ther 2015; 9: 3497-3506
  • 142 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 (33) 23111-23118
  • 143 Nomura S, Tandon NN, Nakamura T, Cone J, Fukuhara S, Kambayashi J. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 2001; 158 (02) 277-287
  • 144 Wang JG, Williams JC, Davis BK. et al. Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner. Blood 2011; 118 (08) 2366-2374
  • 145 Halim AT, Ariffin NA, Azlan M. Review: the multiple roles of monocytic microparticles. Inflammation 2016; 39 (04) 1277-1284
  • 146 Brown GT, McIntyre TM. Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich microparticles. J Immunol 2011; 186 (09) 5489-5496
  • 147 Mause SF, von Hundelshausen P, Zernecke A, Koenen RR, Weber C. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25 (07) 1512-1518
  • 148 Jy W, Mao WW, Horstman L, Tao J, Ahn YS. Platelet microparticles bind, activate and aggregate neutrophils in vitro. Blood Cells Mol Dis 1995; 21 (03) 217-231 , discussion 231a
  • 149 Gasser O, Schifferli JA. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 2004; 104 (08) 2543-2548
  • 150 Dalli J, Norling LV, Renshaw D, Cooper D, Leung KY, Perretti M. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood 2008; 112 (06) 2512-2519
  • 151 Bardelli C, Amoruso A, Federici Canova D. et al. Autocrine activation of human monocyte/macrophages by monocyte-derived microparticles and modulation by PPARγ ligands. Br J Pharmacol 2012; 165 (03) 716-728
  • 152 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104 (22) 2649-2652
  • 153 Martínez MC, Tesse A, Zobairi F, Andriantsitohaina R. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 2005; 288 (03) H1004-H1009
  • 154 Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol 2004; 286 (05) H1910-H1915
  • 155 Mostefai HA, Agouni A, Carusio N. et al. Phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells. J Immunol 2008; 180 (07) 5028-5035
  • 156 Martinez MC, Andriantsitohaina R. Microparticles in angiogenesis: therapeutic potential. Circ Res 2011; 109 (01) 110-119
  • 157 Kim HK, Song KS, Chung JH, Lee KR, Lee SN. Platelet microparticles induce angiogenesis in vitro. Br J Haematol 2004; 124 (03) 376-384
  • 158 Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat-George F. Extracellular vesicles in angiogenesis. Circ Res 2017; 120 (10) 1658-1673
  • 159 Taraboletti G, D'Ascenzo S, Borsotti P, Giavazzi R, Pavan A, Dolo V. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 2002; 160 (02) 673-680
  • 160 Agouni A, Mostefai HA, Porro C. et al. Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. FASEB J 2007; 21 (11) 2735-2741
  • 161 Noren Hooten N, Evans MK. Extracellular vesicles as signaling mediators in type 2 diabetes mellitus. Am J Physiol Cell Physiol 2020; 318 (06) C1189-C1199
  • 162 Pawlowski CL, Li W, Sun M. et al. Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis. Biomaterials 2017; 128: 94-108
  • 163 Patel DB, Santoro M, Born LJ, Fisher JP, Jay SM. Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment. Biotechnol Adv 2018; 36 (08) 2051-2059
  • 164 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 (01) 16-22
  • 165 Nomura S, Shouzu A, Omoto S, Nishikawa M, Iwasaka T. Effects of losartan and simvastatin on monocyte-derived microparticles in hypertensive patients with and without type 2 diabetes mellitus. Clin Appl Thromb Hemost 2004; 10 (02) 133-141
  • 166 Nomura S, Shouzu A, Omoto S, Nishikawa M, Fukuhara S, Iwasaka T. Effect of valsartan on monocyte/endothelial cell activation markers and adiponectin in hypertensive patients with type 2 diabetes mellitus. Thromb Res 2006; 117 (04) 385-392
  • 167 Zhao H, Shang Q, Pan Z. et al. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes 2018; 67 (02) 235-247
  • 168 Sun Y, Shi H, Yin S. et al. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-cell destruction. ACS Nano 2018; 12 (08) 7613-7628
  • 169 Tsukita S, Yamada T, Takahashi K. et al. MicroRNAs 106b and 222 improve hyperglycemia in a mouse model of insulin-deficient diabetes via pancreatic β-cell proliferation. EBioMedicine 2017; 15: 163-172
  • 170 Freyssinet JM, Toti F. Formation of procoagulant microparticles and properties. Thromb Res 2010; 125 (Suppl. 01) S46-S48
  • 171 Słomka A, Urban SK, Lukacs-Kornek V, Żekanowska E, Kornek M. Large extracellular vesicles: have we found the Holy Grail of inflammation?. Front Immunol 2018; 9: 2723
  • 172 Ardoin SP, Shanahan JC, Pisetsky DS. The role of microparticles in inflammation and thrombosis. Scand J Immunol 2007; 66 (2-3): 159-165
  • 173 Andonegui G, Kerfoot SM, McNagny K, Ebbert KV, Patel KD, Kubes P. Platelets express functional toll-like receptor-4. Blood 2005; 106 (07) 2417-2423
  • 174 Chironi G, Simon A, Hugel B. et al. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2775-2780
  • 175 Cherian P, Hankey GJ, Eikelboom JW. et al. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Stroke 2003; 34 (09) 2132-2137
  • 176 Bernal-Mizrachi L, Jy W, Fierro C. et al. Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes. Int J Cardiol 2004; 97 (03) 439-446
  • 177 Diehl P, Aleker M, Helbing T. et al. Increased platelet, leukocyte and endothelial microparticles predict enhanced coagulation and vascular inflammation in pulmonary hypertension. J Thromb Thrombolysis 2011; 31 (02) 173-179
  • 178 Bakouboula B, Morel O, Faure A. et al. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am J Respir Crit Care Med 2008; 177 (05) 536-543
  • 179 Agouni A, Lagrue-Lak-Hal AH, Ducluzeau PH. et al. Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am J Pathol 2008; 173 (04) 1210-1219
  • 180 Amabile N, Cheng S, Renard JM. et al. Association of circulating endothelial microparticles with cardiometabolic risk factors in the Framingham Heart Study. Eur Heart J 2014; 35 (42) 2972-2979
  • 181 Headland SE, Jones HR, Norling LV. et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med 2015; 7 (315) 315ra190
  • 182 Knijff-Dutmer EA, Koerts J, Nieuwland R, Kalsbeek-Batenburg EM, van de Laar MA. Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Arthritis Rheum 2002; 46 (06) 1498-1503
  • 183 González-Quintero VH, Smarkusky LP, Jiménez JJ. et al. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. Am J Obstet Gynecol 2004; 191 (04) 1418-1424
  • 184 Redman CW, Sargent IL. Microparticles and immunomodulation in pregnancy and pre-eclampsia. J Reprod Immunol 2007; 76 (1-2): 61-67
  • 185 Minagar A, Jy W, Jimenez JJ. et al. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology 2001; 56 (10) 1319-1324
  • 186 Marcos-Ramiro B, Oliva Nacarino P, Serrano-Pertierra E. et al. Microparticles in multiple sclerosis and clinically isolated syndrome: effect on endothelial barrier function. BMC Neurosci 2014; 15: 110
  • 187 Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost 2013; 11 (02) 223-233
  • 188 Goubran H, Sabry W, Kotb R, Seghatchian J, Burnouf T. Platelet microparticles and cancer: an intimate cross-talk. Transfus Apheresis Sci 2015; 53 (02) 168-172
  • 189 Tantawy AA, Adly AA, Ismail EA, Habeeb NM, Farouk A. Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: relation to cardiovascular complications. Platelets 2013; 24 (08) 605-614
  • 190 van Beers EJ, Schaap MC, Berckmans RJ. et al; CURAMA study group. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease. Haematologica 2009; 94 (11) 1513-1519
  • 191 Amabile N, Guérin AP, Leroyer A. et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 2005; 16 (11) 3381-3388
  • 192 Carvalho LML, Ferreira CN, Sóter MO. et al. Microparticles: inflammatory and haemostatic biomarkers in polycystic ovary syndrome. Mol Cell Endocrinol 2017; 443: 155-162
  • 193 Chirinos JA, Heresi GA, Velasquez H. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45 (09) 1467-1471
  • 194 Campello E, Spiezia L, Radu CM. et al. Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism. Thromb Res 2011; 127 (05) 473-477
  • 195 Ayers L, Ferry B, Craig S, Nicoll D, Stradling JR, Kohler M. Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea. Eur Respir J 2009; 33 (03) 574-580
  • 196 Maruyama K, Morishita E, Sekiya A. et al. Plasma levels of platelet-derived microparticles in patients with obstructive sleep apnea syndrome. J Atheroscler Thromb 2012; 19 (01) 98-104