Mini Review Open Access
The number of red blood cell-derived microparticles in predicting periprocedural adverse effects in acute STsegment elevation myocardial infarction patients
Alexander E Berezin*
Professor, Consultant of Therapeutic Unit, Department of Internal Medicine, Medical University, Zaporozhye, Ukraine
*Corresponding author: Alexander E Berezin, Professor, Consultant of Therapeutic Unit, Department of Internal Medicine, Medical University, Private Hospital “Vita-Center”, Zaporozhye, Ukraine. Tel: +380612894585; E-mail: @, @
Received:December 27, 2016; Accepted: January 02, 2017; Published: January 10, 2017
Citation: Berezin AE (2017) The number of red blood cell-derived microparticles in predicting periprocedural adverse effects in acute ST-segment elevation myocardial infarction patients. J Clin Trial Cardiol 4(1): 1-6.
The role of the circulating number of Red Blood Cell (RBC) Microparticles (MPs) as predictive biomarker in acute myocardial infarction patients after primary Percutaneous Coronary Intervention (PCI) is widely argued. There are commonly used cardiac biomarkers (i.e., troponins, creatine kinase-myocardial band isoenzymes, myoglobin, heart-type fatty acid-binding protein, copeptin and B-type natriuretic peptide), which have now exhibited broad spectrum limitations regarding short-term and long-termterm mortality rates. Recent clinical studies have shown that the number of RBC-MPs has increased in acute myocardial infarction as compared to healthy volunteers and patients with unstable angina, associated with the extent of myocardial damage and have potential adverse vascular and thrombotic effects. It has been suggested that the number of RBC-MPs might be better predictor compared to other cardiac biomarkers in scintigraphically measured infarct size, periprocedural left ventricular ejection fraction and survival rate.

Keywords: Acute Myocardial Infarction; Primary Percutaneous Coronary Intervention; Cardiac Biomarkers; Red Blood Cell Microparticles; Prognosis;
ATP - Adenosine Tri Phosphate; BNP - Brain Natriuretic Peptide; CFSE - Carboxy Fluorescein Diacetate Succinimidyl Ester CK-MB - Creatine Kinase-Myocardial Band Isoenzyme; EVs - Extracellular Vesicles; ICAM - Intracellular Adhesion Molecule; LVEF - Left Ventricular Ejection Fraction; MPs - Microparticles; PCI - Percutaneous Coronary Intervention; SPRi Microscopy, Nano-Particles- Surface Plasmon Resonance - Based Imaging Microscopy; STEMI, ST - Segment Elevation Myocardial Infarction;VCAM - Vascular Cell Adhesion Molecule;
Microvascular obstruction has remained a prognostic importance for short-term and long-term periprocedural survival after acute ST-Segment Elevation Myocardial Infarction (STEMI) [1, 2]. Although there is a large body of evidence regarding utility of biomarkers of cardiac injury in predicting myocardial functional recovery [3-5], the prognostic information of commonly used cardiac biomarkers (i.e., troponins, creatine kinase-myocardial band isoenzymes (CK-MB), and their combinations) regarding mortality rate is still controversial [6-8]. Indeed, troponin I is an highly sensitive marker of myocardial necrosis or even very minor reversible myocardial injury caused by Percutaneous Coronary Intervention (PCI), which did not influence the death rate [9].

However, in the Selective Inhibition of Delta-protein Kinase C for the Reduction of Infarct Size in Acute Myocardial Infarction (PROTECTION-AMI) trial were determined that only baseline left ventricular ejection fraction (LVEF), infarct size and infarct heterogeneity independently predicted 90-day LVEF, though other biomarkers did not [3]. In the EVOLVE (EValuation Of MCC- 135 for Left VEntricular Salvage in Acute Myocardial Infarction) trial, elevated troponin T level was associated with increased 180-day composite clinical events and independently predicted several adverse events, but not death [10]. In contrast, Gollop et al [11] reported that an elevation in CK-MB was best predictor of adverse events including death compared with troponins in post- PCI individuals.

Thus, actual findings suggest that cardiac biomarker of injury (i.e. troponins, creatinine kinase MB isoenzyme, and probably myoglobin) might no longer be the optimal early predictors in STEMI patients undergoing primary PCI, while they are able to depict worsening myocardial perfusion, myocardial infarct size, cardiac function and postponed left ventricular remodeling. Moreover, as a prognostic marker, CK-MB isoenzyme measured on admission was superior to cardiac troponin using a highsensitivity assay, NTpro-Brain Natriuretic Peptide (BNP) measurement on admission, but myoglobin, heart-type fatty acid-binding protein, copeptin and B-type natriuretic peptide were prognostically equivalent [12]. Consequently, to improve predictive approaches based on biomarker measurement in PCI patients, discovery of novel biomarkers maximally attributed solely to each individual after PCI is required.

Formerly cell-derived microparticles (MPs) were determined as cell debris without any diagnostic and predictive information, but now they are considered biomarkers in cardiovascular and metabolic disease including atherosclerosis, unstable angina pectoris, hypertension, heart failure, arrhythmia, thromboembolism, metabolic syndrome, and diabetes, as well as in subjects with implanted cardiac assist devices [11, 13-22]. The aim of the mini review is to discuss possibilities of use of the red blood cell-derived MPs in predicting of PCI-related complications in STEMI patients.
Definition of MPs
MPs are defined a heterogeneous sub-population of Extracellular Vesicles (EVs) with diameter average from 100 to1000 nm originated from plasma membranes of mother’ cells. EVs are phospholipid-based endogenously produced particles (30-1000 nm in diameter), which contain cell-specific collections of proteins, glycoproteins, lipids, nucleic acids and other molecules. Abundant cells including cardiomyocites, blood cells, endothelial cells, immune cells, and even tumor cells are capable to secrete MPs of different size and compositions [23].

Depending on their origin EVs are graduated to follow subsets, i.e. the exosomes (30–100 nm in diameter), the microvesicles (50–1000 nm in diameter), ectosomes (100–350 nm in diameter), small-size MPs (< 50 nm in diameter) known as membrane particles and apoptotic bodies (1-5 μm in diameter). The exosomes are formed by inward budding of the endosomal membrane and are released on the exocytosis of multivesicular bodies known as late endosomes, whereas the microvesicles are attributed via budding from plasma membranes. However, the exosomes have been predominantly labeled in the case of immune cells (macrophages, T cells, B cells and dendritic cells) and tumor cells. Unlike the exosomes, the ectosomes are ubiquitous microvesicles assembled at and released from the plasma membrane [24].

MPs are released by cellular vesiculation and fission of the membrane of cells [25]. Under normal physiological condition a phospholipid bilayer of plasma membrane of cells represented phosphatidylserine and phosphatidylethanoalamine in inner leaflets, whereas phosphatidylcholine and sphingomyelin represent in the external leaflets. The asymmetrical distribution of phospholipids in the plasma membrane is supported by activity of three major intracellular ATP-dependent enzyme systems, i.e. flippase, floppase, and scramblase. Because aminophospholipids are negatively charged, but phospholipids exhibit neutral charge, the main role of intracellular enzyme systems is supporting electrochemical gradient. Both flippase and floppase belong to family of ATP-dependent phospholipid translocases.

The flippase translocates phosphatidylserine and phosphatidylethanoalamine from the external leaflets to the inner one. The floppase transports phospholipids in the opposite direction. Finally, scramblase being to Ca2+-dependent enzyme system exhibits unspecifically ability of moving of phospholipids between both leaflets of plasma membrane.

Importantly, disappearing of the asymmetrical phospholipid distribution in the bilayer of the cell membrane is considered a clue for vesiculation and forming of MPs. Indeed, both processes of apoptosis or cell activation are required asymmetry in phospholipid distribution that leads to cytoskeleton modifications, membrane budding and MPs release. The mechanisms of vesiculation affect genome and may mediate by some triggers including inflammation [26], while in some cases there is a spontaneous release of MPs from stable cells or due to injury from necrotic cells or from mechanically damaged cells. Particularly, the MPs are released in both constitutive and controlled manners, regulated by intercellular Ca2+ and Rab-GTP-ases and activation of μ-calpain. μ-Calpain is a Ca2+- dependent cytosolic enzyme belong to protease, which cleaves talin and α-actin, leading to decreased binding of integrins to the cytoskeleton and a reduction in cell adhesion and integrity. Finally, interaction of the actin and myosin is a main component for cytoskeleton modification that creates a contractile force and drives the formation of membrane MPs.

Recently MPs are considered a cargo for various molecules. Indeed, MPs carry proteins, RNA, micro-RNA, and DNA fragments from their cells of origin to other parts of the body via blood and other body fluids. Within last decade it has become to know that MPs would act as information transfer for target cells. However, the difference between innate mechanisms affected the release of MPs from stable cells, activated cells or apoptotic cells is yet not fully investigated and requires more studies.

The majority (more than 90%) of MPs in healthy controls are of platelet origin, whereas less than 10% originate from granulocytes and less than 5% from endothelial cells, red blood cells and monocytes [27]. Since all types of particles contain surface proteins derived from their cell of origin (including antigen-presenting cells), while there are additional biomarkers confirming origin of the MPs. The key features of several MP populations are reported in Table 1.
Biological role and function of MPs
MPs have great potentiality in material science- based applications [28], while initially they were recognized as cell debris beyond any biological function. Developments of technologies that attenuate recognize, determination, and measurements of MPs obtained from various cells appear to be indispensable tool to clinical medicine [29].

Recent investigations have been shown that MPs are a universal biological system with an adaptive cellular response to endogenous or external physiological or stressful stimuli and a genius means for intercellular, inter-organ and even inter-organism communication. MPs as derivate of cellular membrane are discussed powerful paracrine regulators of target cell functions [30-32]. Indeed, MPs possess a wide spectrum of biological effects on intercellular communication by transferring different molecules (autoantigens, cytokines, mRNA, iRNA, hormones, tissue coagulation factors, and surface receptors) able to modulate other cells affected growth of tissue, reparation, vasculogenesis, inflammation, apoptosis, infection,
Table 1: Key features of MP populations

Types of MPs



Derived from resting or activated cells


CD24+CD11c− CD66b / CD66acde

Flow cytometry western blotting, mass spectrometry, electron microscopic technique, SPRi microscopy









CD11b+ CD64+/− Ly6Clo

Endothelial cells

CD144, CD62E

T cells

CD4 or CD8

B cells


Dendritic cells

CD1a, CD14, CD141, CD80, CD85, CD86

ICAM(+) cells





CD41 and/or CD61


CD235a, CD44, CD47, CD55, CFSE, annexin V and anti-glycophorin A

Derived from activated or tumor cells

Annexin V binding, CD63, CD81, CD9, LAMP1 and TSG101

Flow cytometry, capture based assays

Derived from apoptotic cells

Annexin V, DNA content, histones

Flow cytometry

Abbreviations: ICAM - Intracellular Adhesion Molecule; VCAM - Vascular Cell Adhesion Molecule; SPRi microscopy; nano-particlessurface plasmon resonance - based imaging microscopy; CFSE – Carboxy Fluorescein Diacetate Succinimidyl Ester;
and malignancy [33-39]. Moreover, RBC-MPs act as NO promoter exerted an erythrocrine function by synthesizing, transporting and releasing NO metabolic products contributing in regulation of vascular tone.
However, MPs are not only cargo for biological active substances. Growing evidence supports the idea that regarding association between immune pattern of MPs originated from different cells (RBCs, endothelial cells, mononuclears, dendritic cells, platelets) and nature evolution of various diseases including CV diseases, cancer, sepsis, eclampsia, autoimmune and metabolic states, etc. [40-33].

RBCs-derived MPs may provide an additional pro-coagulant phospholipid surface enabling the assembly of the clotting enzymes complexes and thrombin generation [44-45]. It has noted the release or recruitment of pro-coagulant MPs at sites of endothelium injury or worsening of integrity through P-selectin pathway could be enhanced or triggered by tissue factor activity [46]. Converging evidences from experimental or clinical data highlight a role for MP harboring tissue factor in the initiation of disseminated intravascular coagulopathy.

The majority investigations have now addressed to the endothelial cell-derived MPs, which are marker of endothelial dysfunction and cardiovascular death [47, 48], while MPs originated from other cells (i.e. red blood cells) have exhibited a relation to severity of atherosclerosis and coronary obstruction [49]. Recent studies have shown that the circulating number of endothelial cell-derived MPs originated from activated or apoptotic cells may be markers with powerful independent predictive value in patients with acute myocardial infarction after PCI, although utility of endothelial cell-derived MP measurement is not strongly determined [50]. However, it has suggested that endothelial cell-derived MP assay could be incorporated into multiple biomarkers strategy based on troponins and creatinine kinase MB isoenzyme measurement to improve risk stratification for cardiovascular events in patients at high risk for cardiac death and cardiovascular events [51].The red blood cell-derived MPs in myocardial infarction

The number of Red Blood Cell (RBC) MPs has increased in acute myocardial infarction as compared to healthy volunteers and patients with unstable angina and probably associated with the extent of myocardial damage. Wang L et al [52] have reported that the baseline levels of MPs received from peripheral red blood cells were significantly higher in the none- ST elevation myocardial infarction (none-STEMI) patients than in healthy controls. Moreover, after PCI and stent implantation, a remarkable increase of RBC-MPs was observed. Specifically, the peak concentration of RBC-MPs was determined at 18 hours following stent implantation. Authors have pointed that the circulating RBC-MPs might cooperate with other MPs mostly derived from platelets and leukocytes and contribute to markedly shortened coagulation time and sufficiently increasing thrombin and fibrin generation after PCI. In ST elevation myocardial infarction (STEMI) patients treated with primary circulating level of PCI RBC-MPs have exhibited significant approximately double elevation compared to volunteers. Moreover, the concentration of PCI RBC-MPs appears to be strongly positively associated with adverse clinical events in short-term follow-up [53].

There is evidence regarding close relationship between circulating number of RBC-MPs and biochemical infarct size, circulating troponins, associate with microvascular obstruction and reverse of ischemia-induced myocardial dysfunction [53], although the exact pathophysiologic routes for these interactions remain to be uncertain. Probably, the pro-coagulant activity of RBC-MPs seems to provide beneficial intrinsic and extrinsic clotting in patients after primary PCI. Indeed, pro-coagulant thrombotic activity of RBC-MPs and their ability inducing platelet activation and aggregation might explain the role of them in the pathogenesis of periprocedural microvascular obstruction and left ventricular remodeling [54, 55]. Therefore, RBC-MPs are able to activate endothelium in visceral organs and thereby influence vasoconstriction and direct injury of them [56, 57]. In this context, RBC-MPs measured in the peripheral blood may be sensitive markers of the thrombo-occlusive vascular process developing in the coronary arteries of STEMI-patients [58, 59]. Although RBC-MPs have usually not been incorporated into predictive analysis due their small sizes and limited resolution of traditional equipment, their relations to the biomarker of cardiovascular repair and their impact on prognosis after primary PCI in STEMI subjects and probably in non-STEMI patients appears to be plenty promising.

Moving across this issue, it would be suggested that RBC-MPs as a player in the myocardial reperfusion injury might attenuate the benefit of PCI after acute myocardial infarction. Whether RBC-MPs would be potentially useful for risk stratification after primary PCI is not fully clear. Therefore, it is not understood whether RBC-MP count would be prognostically superior to highsensitivity cardiac troponins, creatinine kinase MB isoenzyme, myoglobin, natriuretic peptides, copeptine, heart-type fatty acidbinding protein, and scintigraphically measured infarct size, which remains a better correlate of 1-year mortality than either biomarkers. However, measurement of circulating RBC-MP number after primary PCI appears to be promising because lack of individualized biomarkers with predictive value regarding survival in subjects with microvascular obstruction remains to be challenged. All these findings require more investigations in future.
There are no strong evidence regarding the advantages of periprocedural use of RBC-MPs compared to widely used biomarkers including high-sensitivity cardiac troponins, creatinine kinase MB isoenzyme during PCI to provide prognostic information about the degree of myocardial injury and risk of morbidity and mortality. However, the need of discovery of novel biomarker with higher predictive value is obvious fact. RBC-MPs could be discussed as attempt to individualize risk stratification amongst acute ST-segment elevation myocardial infarction patients after primary PCI, because other routinely used biomarkers have exhibited some serious limitations. In future more investigations are required to explain in detail the role of the number of RBCMPs in prediction of survival amongst acute ST-segment elevation myocardial infarction patients after primary PCI.
  1. Crimi G, Pica S, Raineri C, Bramucci E, De Ferrari GM, Klersy C, et al. Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC Cardiovasc Interv. 2013;6(10):1055-1063. doi: 10.1016/j.jcin.2013.05.011.
  2. Brener SJ, Maehara A, Dizon JM, Fahy M, Witzenbichler B, Parise H, et al. Relationship between myocardial reperfusion, infarct size, and mortality: the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction) trial. JACC Cardiovasc Interv. 2013;6(7):718-724. doi: 10.1016/j.jcin.2013.03.013.
  3. Grover S, Bell G, Lincoff M, Jeorg L, Madsen PL, Huang S, et al. Utility of CMR Markers of Myocardial Injury in Predicting LV Functional Recovery: Results from PROTECTION AMI CMR Sub-study. Heart Lung Circ. 2015;24(9): 891-897. doi: 10.1016/j.hlc.2015.03.001.
  4. Loeb HS, Liu JC. Frequency, risk factors, and effect on long-term survival of increased troponin I following uncomplicated elective percutaneous coronary intervention. Clin Cardiol. 2010;33(12):E40-4. doi: 10.1002/clc.20425.
  5. Natarajan MK, Kreatsoulas C, Velianou JL, Mehta SR, Pericak D, Goodhart DM. Incidence, predictors, and clinical significance of troponin-I elevation without creatine kinase elevation following percutaneous coronary interventions. Am J Cardiol. 2004;93(6):750-753.
  6. Jang JS, Jin HY, Seo JS, Yang TH, Kim DK, Kim DS, et al. Prognostic value of creatine kinase-myocardial band isoenzyme elevation following percutaneous coronary intervention: a meta-analysis. Catheter Cardiovasc Intervent. 2012;81(6):959-967.
  7. Testa L, Van Gaal WJ, Biondi Zoccai GG, Agostoni P, Latini RA, Bedogni F, et al. Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition. QJM. 2009;102(6):369-378. doi: 10.1093/qjmed/hcp005.
  8. Cavallini C, Savonitto S, Violini R, Arrraiz G, Plebani M, Olivari Z, et al. Impact of the elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study. Eur Heart J. 2005;26(15):1494-1498.
  9. Chia S, Senatore F, Raffel OC, Lee H, Wackers FJ, Jang IK. Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2008;1(4):415-423. doi: 10.1016/j.jcin.2008.04.010.
  10. Gollop ND, Dhullipala A, Nagrath N, Myint PK. Is periprocedural CK-MB a better indicator of prognosis after emergency and elective percutaneous coronary intervention compared with post-procedural cardiac troponins? Interact Cardiovasc Thorac Surg. 2013;17(5):867-871. doi: 10.1093/icvts/ivt303.
  11. Thulin Å, Christersson C, Alfredsson J, Siegbahn A. Circulating cell-derived microparticles as biomarkers in cardiovascular disease. Biomark Med. 2016;10(9):1009-1022. doi: 10.2217/bmm-2016-0035.
  12. Collinson PO, Gaze DC, Thokala P, Goodacre S. Randomised Assessment of Treatment using Panel Assay of Cardiac markers - Contemporary Biomarker Evaluation (RATPAC CBE). Health Technol Assess. 2013;17(15):v-vi, 1-122. doi: 10.3310/hta17150.
  13. Berezin AE, Kremzer AA, Martovitskaya YV, Berezina TA, Gromenko EA. Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction. EBioMedicine. 2016;4:86-94. doi: 10.1016/j.ebiom.2016.01.018.
  14. Berezin AE, Kremzer AA, Berezina TA, Martovitskaya YV. Pattern of circulating microparticles in chronic heart failure patients with metabolic syndrome: Relevance to neurohumoral and inflammatory activation. BBA Clin. 2015;4:69-75.
  15. Berezin AE, Kremzer AA, Cammarota G, Zulli A, Petrovic D, Martell-Claros N, et al. Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure. Clin Chem Lab Med. 2016;54(7):1259-1267. doi: 10.1515/cclm-2015-0605.
  16. Berezin AE, Kremzer AA, Berezina TA, Martovitskaya Yu V. The pattern of circulating microparticles in patients with diabetes mellitus with asymptomatic atherosclerosis. Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine. 2016;71(1):38-45. doi: 10.1080/17843286.2015.1110894.
  17. Berezin AE, Kremzer AA, Martovitskaya YV, Samura TA, Berezina TA, Zulli A, et al. The utility of biomarker risk prediction score in patients with chronic heart failure. Int J Clin Exp Med. 2015;8(10):18255-18264.
  18. Berezin AE, Kremzer AA, Martovitskaya YV, Samura TA, Berezina TA. The predictive role of circulating microparticles in patients with chronic heart failure. BBA Clin. 2014;3:18-24. doi: 10.1016/j.bbacli.2014.11.006.
  19. Berezin AE. Biomarkers for cardiovascular risk in patients with diabetes. Heart. 2016;102(24):1939-1941.
  20. Jeske WP, Walenga JM, Menapace B, Schwartz J, Bakhos M. Blood cell microparticles as biomarkers of hemostatic abnormalities in patients with implanted cardiac assist devices. Biomark Med. 2016;10(10):1095-1104.
  21. Baron M, Boulanger CM, Staels B, Tailleux A. Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation? J Cell Mol Med. 2012;16(7):1365-1376. doi: 10.1111/j.1582-4934.2011.01486.x.
  22. Berezin A, Zulli A, Kerrigan S, Petrovic D, Kruzliak P. Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases. Clin Biochem. 2015;48(9):562-568. doi: 10.1016/j.clinbiochem.2015.02.003.
  23. Berezin A. Endothelial Derived Micro Particles: Biomarkers for Heart Failure Diagnosis and Management. J Clin Trial Cardiol. 2015;2(3):1-3.
  24. Cocucci E, Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015;25(6):364-372. doi: 10.1016/j.tcb.2015.01.004.
  25. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255-289. doi: 10.1146/annurev-cellbio-101512-122326.
  26. Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2007;21(3):157-171.
  27. Tesselaar ME, Romijn FP, Van DL, Prins FA, Bertina RM, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost. 2007;5(3):520-527.
  28. Sarkar S, Dasgupta AK. Microparticle of drug and nanoparticle: a biosynthetic route. Pharmacol Res Perspect. 2015; 3(5): e00188. doi: 10.1002/prp2.188.
  29. Gu Z, Jing C, Ying YL, He P, Long YT. In situ high throughput scattering light analysis of single plasmonic nanoparticles in living cells. Theranostics. 2015;5(2):188-195. doi:10.7150/thno.10302.
  30. Gong J, Jaiswal R, Dalla P, Luk F, Bebawy M. Microparticles in cancer: A review of recent developments and the potential for clinical application. Semin Cell Dev Biol. 2015;40:35-40. doi: 10.1016/j.semcdb.2015.03.009.
  31. Das S, Halushka MK. Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc Pathol. 2015; 24(4):199-206. doi: 10.1016/j.carpath.2015.04.007.
  32. Berezin A, Zulli A, Kerrigan S, Petrovic D, Kruzliak P. Predictive role of circulating endothelial-derived microparticles in cardiovascular diseases. Clin Biochem. 2015;48(9):562-568.
  33. Jadli A, Sharma N, Damania K, Satoskar P, Bansal V, Ghosh K, et al. Promising prognostic markers of Preeclampsia: New avenues in waiting. Thromb Res. 2015;136(2):189-195. doi: 10.1016/j.thromres.2015.05.011.
  34. Greening DW, Gopal SK, Mathias RA, Liu L, Sheng J, Zhu HJ, et al. Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin Cell Dev Biol. 2015;40:60-71. doi: 10.1016/j.semcdb.2015.02.008.
  35. Martinez MC, Andriantsitohaina R. Microparticles in angiogenesis: therapeutic potential. Circ Res. 2011;109(1):110-9. doi: 10.1161/CIRCRESAHA.110.233049.
  36. Souza AC, Yuen PS, Star RA. Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and AKI. Kidney Int. 2015;87(6):1100-1108. doi: 10.1038/ki.2015.26.
  37. Neri T, Pergoli L, Petrini S, Gravendonk L, Balia C, Scalise V, et al. Particulate matter induces prothrombotic microparticle shedding by human mononuclear and endothelial cells. Toxicol In Vitro. 2016;32:333-338. doi: 10.1016/j.tiv.2016.02.001.
  38. 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. doi: 10.1111/j.1538-7836.2011.04488.x.
  39. Cordazzo C, Petrini S, Neri T, Lombardi S, Carmazzi Y, Pedrinelli R, et al. Rapid shedding of proinflammatory microparticles by human mononuclear cells exposed to cigarette smoke is dependent on Ca2+ mobilization. Inflamm Res. 2014;63(7):539-547. doi: 10.1007/s00011-014-0723-7.
  40. Li M, Yu D, Williams KJ, Liu ML. Tobacco smoke induces the generation of procoagulant microvesicles from human monocytes/macrophages. Arterioscler Thromb Vasc Biol. 2010;30(9):1818-1824.
  41. Novelli F, Neri T, Tavanti L, Armani C, Noce C, Falaschi F, et al. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study. PLoS One. 2014;9(4):e95013. doi: 10.1371/journal.pone.0095013.
  42. Vatsyayan R, Kothari H, Pendurthi UR, Rao LV. 4-Hydroxy-2-nonenal enhances tissue factor activity in human monocytic cells via p38 mitogen-activated protein kinase activation-dependent phosphatidylserine exposure. Arterioscler Thromb Vasc Biol. 2013;33(7):1601-1611. doi: 10.1161/ATVBAHA.113.300972.
  43. Satta N, Toti F, Feugeas O, Bohbot A, Dachary-Prigent J, Eschwège V, et al. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol. 1994;153(7):3245-3255.
  44. Morel N, Morel O, Delabranche X, Jesel L, Sztark F, Dabadie P, et al. Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes. Ann Fr Anesth Reanim. 2006;25(9):955-966.
  45. Chung SM, Bae ON, Lim KM, Noh JY, Lee MY, Jung YS, et al. Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes. Arterioscler Thromb Vasc Biol. 2007;27(2):414-421.
  46. Kawata J, Aoki M, Ishimaru Y, Ono T, Sagara K, Narahara S, et al. Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase. Blood Cells Mol Dis. 2015;54(2):206-209. doi: 10.1016/j.bcmd.2014.10.005.
  47. Berezin AE. Impaired Phenotype of Circulating Endothelial-Derived Microparticles: Novel Marker of Cardiovascular Risk. Journal of Cardiology and Therapy. 2015;2(4):273-278 doi:10.17554/j.issn.2309-6861.2015.02.77.
  48. Amabile N, Gurin AP, Leroyer A, Mallat Z, Nguyen C, Boddaert J. 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.
  49. Berezin A. The Clinical Utility of Circulating Microparticles’ Measurement in Heart Failure Patients. J Vasc Med Surg. 2016;4(4):275-284.
  50. Berezin AE, Mokhnach RE. The promises, methodological discrepancies and pitfalls in measurement of cell-derived extracellular vesicles in diseases. J Biotechnol Biomater, 2016;6(2):232-239.
  51. Nozaki T, Sugiyama S, Koga H, Sugamura K, Ohba K, Matsuzawa Y. 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;54:601-608. doi: 10.1016/j.jacc.2009.05.022.
  52. Wang L, Yayan Bi, Muhua Cao, Ruishuang Ma, Xiaoming Wu, Yan Zhang, et al. Microparticles and blood cells induce procoagulant activity via phosphatidylserine exposure in NSTEMI patients following stent implantation. International Journal of Cardiology. 2016;223:121-128. doi: 10.1016/j.ijcard.2016.07.260.
  53. Giannopoulos G, Vrachatis DA, Oudatzis G, Paterakis G, Angelidis C, Koutivas A, et al. Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction. Cardiology. 2017;136(1):15-20.
  54. Aung HH, Tung JP, Dean MM, Flower RL, Pecheniuk NM. Procoagulant role of microparticles in routine storage of packed red blood cells: potential risk for prothrombotic post-transfusion complications. Pathology. Pathology. 2017;49(1):62-69. doi: 10.1016/j.pathol.2016.10.001.
  55. Yao Z, Wang L, Wu X, Zhao L, Chi C, Guo L, et al. Enhanced Procoagulant Activity on Blood Cells after Acute Ischemic Stroke. Transl Stroke Res. 2016.
  56. Chang AL, Kim Y, Seitz AP, Schuster RM, Lentsch AB, Pritts TA. Erythrocyte Derived Microparticles Activate Pulmonary Endothelial Cells in a Murine Model of Transfusion. Shock. 2016.
  57. Giannopoulos G, Oudatzis G, Paterakis G, Synetos A, Tampaki E, Bouras G, et al. Red blood cell and platelet microparticles in myocardial infarction patients treated with primary angioplasty. Int J Cardiol. 2014;176(1):145-150. doi: 10.1016/j.ijcard.2014.07.022.
  58. Suades R, Padró T, Crespo J, Ramaiola I, Martin-Yuste V, Sabaté M, et al. Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time. Int J Cardiol. 2016;202:378-387. doi: 10.1016/j.ijcard.2015.09.011.
  59. Berezin AE, Kremzer AA, Samura TA, Martovitskaya YV, Malinovskiy YV, Oleshko SV, Berezina TA. Predictive value of apoptotic microparticles to mononuclear progenitor cells ratio in advanced chronic heart failure patients. J Cardiol. 2015;65(5):403-411. doi: 10.1016/j.jjcc.2014.06.014.
  60. Hakan TM, Mehmet EK, Enbiya A, Ziya S, Eftal MB, Hamit HA. Oxidative and Antioxidative Status after Successful Percutaneous Transluminal Coronary Angioplasty in Acute Myocardial Infarction. JCTCD. 2014;1(1):1-4. DOI: 6882/1/1/00103
Listing : ICMJE   

Creative Commons License Open Access by Symbiosis is licensed under a Creative Commons Attribution 3.0 Unported License