Involvement of microparticles in diabetic vascular complications

Summary

Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipidbearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the procoagulant state and vascular pathology in patients with T2DM.

keywords

Tissue factor/factor VII - tissue factor pathway inhibitor (TFPI) - diabetes mellitus - endothelial cells - microparticles

• References

• 1 Nomura DS. Dynamic role of microparticles in type 2 diabetes mellitus. Curr Diabetes Rev 2009; 5: 245-251.
• 2 Barillari G, Fabbro E, Pasca S. et al. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. Blood Coagul Fibrinolysis 2009; 20: 290-296.
• 3 Erem C, Hacihasanogju A, Celik S. et al. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications. Med Princ Pract 2005; 14: 22-30.
• 4 Boden G, Vaidyula VR, Homko C. et al. 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: 4352-4358.
• 5 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: 165-172.
• 6 Feng B, Chen Y, Luo Y. et al. Circulating level of microparticles and their correlation with arterial elasticity and endothelium-dependent dilation in patients with type 2 diabetes mellitus. Atherosclerosis 2010; 208: 264-269.
• 7 Diamant M, Tushuizen ME, Sturk A. et al. Cellular microparticles: new players in the field of vascular disease?. Eur J Clin Invest 2004; 34: 392-401.
• 8 Leroyer AS, Tedgui A, Boulanger CM. Role of microparticles in atherothrombosis. J Intern Med 2008; 263: 528-537.
• 9 Hugel B, Martinez MC, Kunzelmann C. et al. Membrane microparticles: two sides of the coin. Physiology (Bethesda) 2005; 20: 22-27.
• 10 Aharon A, Tamari T, Brenner B. Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells. Thromb Haemost 2008; 100: 878-885.
• 11 Daubie V, Pochet R, Houard S. et al. Tissue factor: a mini-review. J Tissue Eng Regen Med 2007; 1: 161-169.
• 12 Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med 2004; 10: 171-178.
• 13 Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359: 938-949.
• 14 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: 75-84.
• 15 Diamant M, Nieuwland R, Pablo RF. et al. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002; 106: 2442-2447.
• 16 Morishita E, Asakura H, Jokaji H. et al. Hypercoagulability and high lipoprotein (a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996; 120: 7-14.
• 17 Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes 1997; 46 (Suppl. 02) S31-37.
• 18 Malmström RE, Settergren M, Böhm F. et al. No effect of lipid lowering on platelet activity in patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance. Thromb Haemost 2009; 101: 157-164.
• 19 van Werkum JW, Topcu Y, Postma S. et al. Effects of diabetes mellitus on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel. Thromb Haemost 2008; 99: 637-639.
• 20 Carnethon MR, Biggs ML, Barzilay J. et al. Diabetes and coronary heart disease as risk factors for mortality in older adults. Am J Med 2010; 123: 556. e1-9.
• 21 Emerging Risk Factors Collaboration. Sarwar N, Gao P, Seshasai SR. et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375: 2215-2222.
• 22 Nomura S, Inami N, Shouzu A. et al. Correlation and association between plasma platelet-, monocyte- and endothelial cell-derived microparticles in hypertensive patients with type 2 diabetes mellitus. Platelets 2009; 20: 406-414.
• 23 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: 193-201.
• 24 Chahed S, Leroyer AS, Benzerroug M. et al. Increased vitreous shedding of microparticles in proliferative diabetic retinopathy stimulates endothelial proliferation. Diabetes 2010; 59: 694-701.
• 25 El Haouari M, Rosado JA. Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review. Blood Cells Mol Dis 2008; 41: 119-123.
• 26 Vinik AI, Erbas T, Park TS. et al. Platelet dysfunction in type 2 diabetes. Diabetes Care 2001; 24: 1476-1485.
• 27 Zwaal RF, Comfurius P, Bevers EM. Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci 2005; 62: 971-988.
• 28 Hamed S, Brenner B, Abassi Z. et al. Hyperglycemia and Oxidized-LDL exert a deleterious effect on Endothelial Progenitor Cell migration in Type 2 Diabetes Mellitus. Thromb Res 2010; 126: 166-174.
• 29 DeLisser HM, Christofidou-Solomidou M, Strieter RM. et al. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 1997; 151: 671-677.
• 30 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: 1622-1630.
• 31 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: 429-435.
• 32 Aharon A, Katzenell S, Tamari T. et al. Microparticles bearing tissue factor and tissue factor pathway inhibitor in gestational vascular complications. J Thromb Haemost 2009; 7: 1047-1050.
• 33 Yuana Y, Bertina RM, Osanto S. Pre-analytical and analytical issues in the analysis of blood microparticles. Thromb Haemost 2010; 105: 396-408.
• 34 Del Conde I, Shrimpton CN, Thiagarajan P. et al. Tissue-factor bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106: 1604-1611.
• 35 Scholz T, Temmler U, Krause S. et al. Transfer of tissue factor from platelets to monocytes: role of platelet-derived microvesicles and CD62P. Thromb Haemost 2002; 88: 1033-1038.
• 36 DeVenecia G, Davis MD. Histology and fluorescein angiography of microaneurysms in diabetes mellitus. Invest Ophthalmol 1967; 6: 555.
• 37 Kohner EM, Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol 1970; 69: 403-414.
• 38 Movahed MR, Hashemzadeh M, Jamal MM. The prevalence of pulmonary embolism and pulmonary hypertension in patients with type II diabetes mellitus. Chest 2005; 128: 3568-3571.
• 39 Ageno W, Becattini C, Brighton T. et al. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 2008; 117: 93-102.
• 40 Leroyer AS, Tedgui A, Boulanger CM. Microparticles and type 2 diabetes. Diabetes Metab 2008; 34: S27-32.
• 41 Brill A, Dashevsky O, Rivo J. et al. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 2005; 67: 30-38.
• 42 Mause SF, Ritzel E, Liehn EA. et al. Platelet microparticles enhance the vasoregen-erative potential of angiogenic early outgrowth cells after vascular injury. Circulation 2010; 122: 495-506.
• 43 Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med 2010; 38: S26-34.
• 44 Mackman N. On the trail of microparticles. Circ Res 2009; 104: 925-927.
• 45 Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37: 1528-1542.
• 46 L’Abbate A. Large and micro coronary vascular involvement in diabetes. Pharmacol Rep. 2005; 57 (Suppl) 3-9.
• 47 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124 (Suppl. 03) 58S-68S.