Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

Microvesicles (MVs), also known as microparticles, are small membrane vesicles released from different cell types under different conditions. MVs have been detected in the circulation and in organs/tissues in various diseases, including diabetes. Patients with different types of diabetes and complications have different cellular MV patterns. Studies have shown that MVs may mediate vascular thrombosis, vascular inflammation, angiogenesis, and other pathological processes of the disease through their procoagulant, pro-inflammatory, pro-angiogenic, proteolytic, and other properties. Therefore, MVs contribute to the development of diabetic macrovascular and microvascular complications. In addition, clinical studies have indicated that changes in MV number and composition may reflect the pathophysiological conditions of disease, and therefore, may serve as potential biomarkers for diagnostic and prognostic use. Understanding MVs' involvement in the pathophysiological conditions may provide insight into disease mechanisms and would also be helpful for the development of novel therapeutic strategies in the future. Here, we review the latest publications from our group and other groups and focus on the involvement of MVs in diabetic complications.

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[48]  Shao-Sung Huang,et al.  Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria , 2010, Journal of hypertension.

[49]  T. Nawrot,et al.  Air pollution‐associated procoagulant changes: the role of circulating microvesicles , 2012, Journal of thrombosis and haemostasis : JTH.

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[51]  G. Müller,et al.  Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. , 2011, Cellular signalling.

[52]  R. Heine,et al.  Postprandial changes in the phospholipid composition of circulating microparticles are not associated with coagulation activation. , 2012, Thrombosis research.

[53]  T. Lüscher,et al.  AngiomiR-126 expression and secretion from circulating CD34(+) and CD14(+) PBMCs: role for proangiogenic effects and alterations in type 2 diabetics. , 2013, Blood.

[54]  M. Matsumura,et al.  Elevation of monocyte-derived microparticles in patients with diabetic retinopathy. , 2006, Diabetes research and clinical practice.

[55]  S. Nomura,et al.  Correlation and association between plasma platelet-, monocyte- and endothelial cell-derived microparticles in hypertensive patients with type 2 diabetes mellitus , 2009, Platelets.

[56]  G. Nickenig,et al.  Circulating CD 31 1 / Annexin V 1 microparticles correlate with cardiovascular outcomes , 2011 .

[57]  P. Mannucci,et al.  Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay , 2011, Journal of Thrombosis and Thrombolysis.

[58]  R Lacroix,et al.  Impact of pre‐analytical parameters on the measurement of circulating microparticles: towards standardization of protocol , 2012, Journal of thrombosis and haemostasis : JTH.

[59]  T. Iwasaka,et al.  The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients , 2009, Platelets.

[60]  Nizar M. Mhaidat,et al.  The putative diabetic plasma marker, soluble CD36, is non‐cleaved, non‐soluble and entirely associated with microparticles , 2011, Journal of thrombosis and haemostasis : JTH.

[61]  N. Takahashi,et al.  Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes. , 2004, Atherosclerosis.

[62]  M. Hellum,et al.  Anticoagulant effects of an antidiabetic drug on monocytes in vitro. , 2011, Thrombosis research.

[63]  StéphaneRobert,et al.  High-Sensitivity Flow Cytometry Provides Access to Standardized Measurement of Small-Size Microparticles—Brief Report , 2012 .

[64]  S. Spinelli,et al.  A novel method for overexpression of peroxisome proliferator‐activated receptor‐γ in megakaryocyte and platelet microparticles achieves transcellular signaling , 2012, Journal of thrombosis and haemostasis : JTH.

[65]  G. Cimmino,et al.  The missing link between atherosclerosis, inflammation and thrombosis: is it tissue factor? , 2011, Expert review of cardiovascular therapy.

[66]  Nikos Werner,et al.  High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. , 2013, Cardiovascular research.

[67]  M. Matsumura,et al.  Increased levels of platelet-derived microparticles in patients with diabetic retinopathy. , 2005, Diabetes research and clinical practice.

[68]  J. Freyssinet,et al.  Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus , 2004, Thrombosis and Haemostasis.

[69]  Vincenza Dolo,et al.  Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. , 2002, The American journal of pathology.

[70]  X. Chen,et al.  Microvesicle-mediated Transfer of MicroRNA-150 from Monocytes to Endothelial Cells Promotes Angiogenesis* , 2013, The Journal of Biological Chemistry.

[71]  Maarten Hulsmans,et al.  MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease. , 2013, Cardiovascular research.

[72]  P. Hopke,et al.  Effects of outdoor air pollutants on platelet activation in people with type 2 diabetes , 2012, Inhalation toxicology.

[73]  M. Nishikawa,et al.  Significance of chemokines and activated platelets in patients with diabetes , 2000, Clinical and experimental immunology.

[74]  T. Iwasaka,et al.  Detection of monocyte-derived microparticles in patients with Type II diabetes mellitus , 2002, Diabetologia.

[75]  Patrice Darmon,et al.  Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. , 2002, Diabetes.

[76]  T. Iwasaka,et al.  Benidipine improves oxidized LDL-dependent monocyte and endothelial dysfunction in hypertensive patients with type 2 diabetes mellitus , 2005, Journal of Human Hypertension.

[77]  K. Kugiyama,et al.  Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease. , 2006, European heart journal.

[78]  P. Massin,et al.  Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation , 2009, Diabetes.

[79]  B. Cookson,et al.  Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life , 2012, Infection and Immunity.

[80]  S. Nomura,et al.  Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. , 1995, Atherosclerosis.

[81]  A. Harel-Bellan,et al.  Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats , 2011, Molecular vision.

[82]  U. Pendurthi,et al.  Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. , 2004, Blood.

[83]  AndreasSchäfer,et al.  Soluble Guanylyl Cyclase Activation With HMR1766 Attenuates Platelet Activation in Diabetic Rats , 2006 .

[84]  T. Lüscher,et al.  Tissue factor and cardiovascular disease: quo vadis? , 2010, Circulation journal : official journal of the Japanese Circulation Society.

[85]  Tomohiro Sakamoto,et al.  Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. , 2005, Journal of the American College of Cardiology.

[86]  Ming-Lin Liu,et al.  Tobacco Smoke Induces the Generation of Procoagulant Microvesicles From Human Monocytes/Macrophages , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[87]  B. Goichot,et al.  Circulating procoagulant microparticles in obesity. , 2006, Diabetes & metabolism.

[88]  P. Furmanski Revealing the mechanism of tissue damage due to tobacco use: finally, a smoking gun? , 2013, The American journal of pathology.

[89]  T. Iwasaka,et al.  Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus , 2007, Journal of Human Hypertension.

[90]  G. Nickenig,et al.  Circulating CD 31 / Annexin V Apoptotic Microparticles Correlate With Coronary Endothelial Function in Patients With Coronary Artery Disease , 2005 .

[91]  Shusheng Wang,et al.  AngiomiRs--key regulators of angiogenesis. , 2009, Current opinion in genetics & development.

[92]  G. Guan,et al.  Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease , 2012, Diabetes & vascular disease research.

[93]  T. Nakayama,et al.  Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome , 2008, Thrombosis and Haemostasis.

[94]  Subrata Chakrabarti,et al.  MicroRNA-200b Regulates Vascular Endothelial Growth Factor–Mediated Alterations in Diabetic Retinopathy , 2011, Diabetes.

[95]  Didier Revel,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). , 2009, Atherosclerosis.

[96]  T. Iwasaka,et al.  Activated Platelet and Oxidized LDL Induce Endothelial Membrane Vesiculation: Clinical Significance of Endothelial Cell-Derived Microparticles in Patients With Type 2 Diabetes , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[97]  P. Kincaid‐smith,et al.  Localisation of complement components in association with glomerular extracellular particles in various renal diseases , 2005, Virchows Archiv A.

[98]  Daniela Wenzel,et al.  Endothelial Microparticle–Mediated Transfer of MicroRNA-126 Promotes Vascular Endothelial Cell Repair via SPRED1 and Is Abrogated in Glucose-Damaged Endothelial Microparticles , 2013, Circulation.

[99]  G. Fan,et al.  Extracellular/circulating microRNAs and their potential role in cardiovascular disease. , 2011, American journal of cardiovascular disease.

[100]  Jing Li,et al.  Secreted monocytic miR-150 enhances targeted endothelial cell migration. , 2010, Molecular cell.

[101]  S. Nomura,et al.  Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with Type 2 diabetes mellitus. , 2003, Journal of diabetes and its complications.

[102]  E. Mohler,et al.  Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population , 2010, Cytometry. Part B, Clinical cytometry.

[103]  K. Peter,et al.  Circulating microparticles generate and transport monomeric C-reactive protein in patients with myocardial infarction. , 2012, Cardiovascular research.

[104]  AnnaZampetaki,et al.  Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes , 2010 .

[105]  T. Iwasaka,et al.  Effect of Ticlopidine on Monocyte-derived Microparticles and Activated Platelet Markers in Diabetes Mellitus , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[106]  M. Goligorsky,et al.  Endothelium-derived microparticles impair endothelial function in vitro. , 2004, American journal of physiology. Heart and circulatory physiology.

[107]  Nikos Werner,et al.  Circulating CD31+/Annexin V+ Apoptotic Microparticles Correlate With Coronary Endothelial Function in Patients With Coronary Artery Disease , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[108]  D. Johns,et al.  Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. , 2012, The Journal of clinical investigation.

[109]  J. Copeland,et al.  Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation. , 2002, Thrombosis research.

[110]  T. Iwasaka,et al.  Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients , 2009, Journal of Thrombosis and Thrombolysis.

[111]  A. Tedgui,et al.  Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. , 2006, Hypertension.

[112]  D. Hanley,et al.  Antiplatelet profiles of the fixed-dose combination of extended-release dipyridamole and low-dose aspirin compared with clopidogrel with or without aspirin in patients with type 2 diabetes and a history of transient ischemic attack: a randomized, single-blind, 30-day trial. , 2008, Clinical therapeutics.

[113]  G. Müller,et al.  Microvesicles/exosomes as potential novel biomarkers of metabolic diseases , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[114]  R. Nieuwland,et al.  Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus , 2002, Circulation.

[115]  K. Williams,et al.  Novel proteolytic microvesicles released from human macrophages after exposure to tobacco smoke. , 2013, The American journal of pathology.

[116]  J. Hudson,et al.  Platelet microparticle-associated protein disulfide isomerase promotes platelet aggregation and inactivates insulin. , 2008, Biochimica et biophysica acta.

[117]  T. Iwasaka,et al.  Effect of valsartan on monocyte/endothelial cell activation markers and adiponectin in hypertensive patients with type 2 diabetes mellitus. , 2006, Thrombosis research.

[118]  H. K. Kim,et al.  Platelet microparticles induce angiogenesis in vitro , 2004, British journal of haematology.

[119]  Fariborz Mobarrez,et al.  A multicolor flow cytometric assay for measurement of platelet-derived microparticles. , 2010, Thrombosis research.

[120]  N. Mackman,et al.  Pre-analytical and analytical variables affecting the measurement of plasma-derived microparticle tissue factor activity. , 2012, Thrombosis research.

[121]  Kristina M. Little,et al.  The plasma microparticle proteome. , 2010, Seminars in thrombosis and hemostasis.

[122]  H. Lim,et al.  Clinically apparent atherosclerotic disease in diabetes is associated with an increase in platelet microparticle levels , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[123]  S. Nomura,et al.  Effects of miglitol in platelet-derived microparticle, adiponectin, and selectin level in patients with type 2 diabetes mellitus , 2011, International journal of general medicine.

[124]  P. Schauer,et al.  Restoration of glycemic control in patients with type 2 diabetes mellitus after bariatric surgery is associated with reduction in microparticles. , 2013, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[125]  J. Chou,et al.  Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin , 2003, The Journal of experimental medicine.