Membrane microparticles (MP) are released by activated or damaged cells and are able to accelerate blood clotting (coagulation). MP possess coagulation activity since all of them contain on their surface phosphatidylserine (PS), a substrate for the assembly of coagulation complexes, and some of them tissue factor (TF), the primary initiator of coagulation cascade reactions. We compared the coagulation activity and amount of MP in the blood of healthy donors (n=34) and patients with myocardial infarction (MI) (n=32), advanced atherosclerosis (AA) (n=32) and idiopathic pulmonary arterial hypertension (IPAH) (n=19). Total MP fraction was obtained from blood plasma by sedimentation at 20000 g, 30 min. The coagulation activity of PM isolated from 100 μl of donor and patient plasma was determined using a modified recalcification test. MP were added to substrate plasma devoid of endogenous MF, plasma was recalcified, and clotting was recorded by changes in optical density (A450), determining lag phase (min) and maximum rate (Vmax, %A450/min). MP were counted by flow cytometry as PS+ particles (lactadgerin-FITC staining) smaller than 1 μm and their concentration was expressed as 105 MP/μl plasma. MP in all patient groups accelerated plasma clotting more effectively than donor MP. Lag phase compared with donors (11.8 [11.0-13.1] median and interquartile range) was shorter in patients with AA (8.8 [7.0-10.3], p<0.001), MI (9.5 [7.3-12.1], p=0.004), ILAH (9.8 [6.0-12/0], p=0.015), and Vmax compared with donors (13.1 [11.7-13.9]) was higher in patients with AA (20.8 [15.2-25.3], p<0.001), ILAH (17.8 [14.9-22.5], p=0.001), but not MI (12.6 [11.1-15.7], p=0.941). MP concentrations compared with donors (0.59 [0.34-0.78]) were higher in patients with AA (0.74 [0.50-1.18], p=0.004), lower in patients with MI (0.29 [0.23-0.55], p<0.001), and not significantly different in patients with ILAH (0.43 [0.30-0.76], p=0.445). In all groups of patient, there was a significant correlation between MP concentration of and parameters 1/lag phase and Vmax of plasma clotting. The data obtained show that the increase in total coagulation activity of MP can be explained by an increase in their concentration only in patients with AA. Anti-TF antibodies did not alter clotting parameters in the presence of MP from donors and patients, indicating that TF is not involved in the realization of the coagulation properties of the tested MP. At the same time, in all groups of patients there was a significant increase in the expression of PS on the surface of MP compared to donors, which could be one of the reasons for their increased coagulation activity.
Antonova O.A. et al. Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases // Biomeditsinskaya Khimiya. - 2022. - V. 68. -N 4. - P. 288-296.
Antonova O.A. et al., "Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases." Biomeditsinskaya Khimiya 68.4 (2022): 288-296.
Antonova, O. A., Golubeva, N. V., Yakushkin, V. V., Zyuryaev, I. T., Krivosheeva, E. N., Komarov, A. L., Martynyuk, T. V., Mazurov, A. V. (2022). Coagulation activity of circulating membrane microparticles in patients with cardiovascular diseases. Biomeditsinskaya Khimiya, 68(4), 288-296.
References
Owens A.P. 3rd, Mackman N. (2011) Microparticles in hemostasis and thrombosis. Circ. Res., 108, 1284-1297. CrossRef Scholar google search
Mooberry M.J., Key N.S. (2016) Microparticle analysis in disorders of hemostasis and thrombosis. Cytometry A., 89, 111-122. CrossRef Scholar google search
Ridger V.C., Boulanger C.M., Angelillo-Scherrer A., Badimon L., Blanc-Brude O., Bochaton-Piallat M.L., Boilard E., Buzas E.I., Caporali A., Dignat-George F., Evans P.C., Lacroix R., Lutgens E., Ketelhuth D.F.J., Nieuwland R., Toti F., Tunon J., Weber C., Hoefer I.E. (2017) Microvesicles in vascular homeostasis and diseases. Position paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. Thromb. Haemost., 117, 1296-1316. CrossRef Scholar google search
Antonova O.A., Yakushkin V.V., Mazurov A.V. (2019) Coagulation activity of membrane microparticles. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 13(3), 169-186. CrossRef Scholar google search
Khaspekova S.G., Antonova O.A., Shustova O.N., Yakushkin V.V., Golubeva N.V., Titaeva E.V., Dobrovolsky A.B., Mazurov A.V. (2016) Activity of tissue factor in microparticles produced in vitro by endothelial cells, monocytes, granulocytes, and platelets. Biochemistry (Moscow), 81(2), 114-121. CrossRef Scholar google search
Aleman M.M., Gardiner C., Harrison P., Wolberg A.S. (2011) Differential contribution of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability. J. Thromb. Haemost., 9, 2251-2261. CrossRef Scholar google search
van der Meijden P.E., van Schilfgaarde M., van Oerle R., Renné T., ten Cate H., Spronk H.M. (2012) Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J. Thromb. Haemost., 10, 1355-1362. CrossRef Scholar google search
Lipets E.N., Antonova O.A., Shustova O.N., Losenkova K.V., Mazurov A.V., Ataullakhanov F.I. (2020) Use of thrombodynamics for revealing the participation of platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation. PLoS One, 15(5), e0227932. CrossRef Scholar google search
Biasucci L.M., Porto I., di Vito L., de Maria G.L., Leone A.M., Tinelli G., Tritarelli A., di Rocco G., Snider F., Capogrossi M.C., Crea F. (2012) Differences in microparticle release in patients with acute coronary syndrome and stable angina. Circ. J., 76, 2174-2182. CrossRef Scholar google search
Skeppholm M., Mobarrez F., Malmqvist K., Wallén H. (2012) Platelet-derived microparticles during and after acute coronary syndrome. Thromb. Haemost., 107, 1122-1129. CrossRef Scholar google search
Namba M., Tanaka A., Shimada K., Ozeki Y., Uehata S., Sakamoto T., Nishida Y., Nomura S., Yoshikawa J. (2007) Circulating platelet-derived microparticles are associated with atherothrombotic events: a marker for vulnerable blood. Arterioscler. Thromb. Vasc. Biol., 27, 255-256. CrossRef Scholar google search
Montoro-García S., Shantsila E., Tapp L.D., López-Cuenca A., Romero A.I., Hernández-Romero D., Orenes-Piñero E., Manzano-Fernández S., Valdés M., Marín F., Lip G.Y. (2013) Small-size circulating microparticles in acute coronary syndromes: relevance to fibrinolytic status, reparative markers and outcomes. Atherosclerosis, 227, 313-322. CrossRef Scholar google search
Suades R., Padró T., Crespo J., Ramaiola I., Martin-Yuste V., Sabaté M., Sans-Roselló J., Sionis A., Badimon L. (2016) 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., 202, 378-387. CrossRef Scholar google search
Suades R., Padró T., Vilahur G., Martin-Yuste V., Sabaté M., Sans-Roselló J., Sionis A., Badimon L. (2015) Growing thrombi release increased levels of CD235a+ microparticles and decreased levels of activated platelet derived microparticles. Validation in ST-elevation myocardial infarction patient. J. Thromb. Haemost., 13, 1776-1786. CrossRef Scholar google search
Giannopoulos G., Vrachatis D.A., Oudatzis G., Paterakis G., Angelidis C., Koutivas A., Sianos G., Cleman M.W., Filippatos G., Lekakis J., Deftereos S. (2017) Circulating erythrocyte microparticles and the biochemical extent of myocardial injury in ST elevation myocardial Infarction. Cardiology, 136, 15-20. CrossRef Scholar google search
Bernal-Mizrachi L., Jy W., Jimenez J.J., Pastor J., Mauro L.M., Horstman L.L., de Marchena E., Ahn Y.S. (2003) High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am. Heart. J., 145, 962-970. CrossRef Scholar google search
Tan K.T., Tayebjee M.H., Lynd C., Blann A.D., Lip G.Y. (2005) Platelet microparticles and soluble P selectin in peripheral artery disease: relationship to extent of disease and platelet activation markers. Ann Med., 37, 61-66. CrossRef Scholar google search
Crawford1 J.R., Trial1 J., Nambi V., Hoogeveen R.C., Taffet G.E., Entman M.L. (2016) Plasma levels of endothelial microparticles bearing monomeric C-reactive protein are increased in peripheral artery disease. J. Cardiovasc. Trans. Res., 9, 184-193. CrossRef Scholar google search
Amabile N., Heiss Ch., Chang V., Angeli F.S., Damon L., Rame E.J., McGlothlin D., Grossman W., de Marco T., Yeghiazarians Y. (2009) Increased CD62E(+) endothelial microparticle levels predict poor outcome in pulmonary hypertension patients. J. Heart Lung Transplant., 10, 1081-1086. CrossRef Scholar google search
International Society for Extracellular Vesicles (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles., 7(1), 1535750. CrossRef Scholar google search
Muravlev I.A., Antonova O.A., Golubeva N.V., Mazurov A.V. (2021) Platelets activated by different agonists produce microparticles with the same procoagulant properties. Thromb. Res., 207, 123-125. CrossRef Scholar google search
Shustova O.N., Antonova O.A., Golubeva N.V., Khaspekova S.G., Yakushkin V.V., Aksuk S.A., Alchinova I.B., Karganov M.Y., Mazurov A.V. (2017) Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: Impact of active tissue factor. Blood Coagulation Fibrinolysis., 28(5), 373-382. CrossRef Scholar google search
Osterud B., Bjorklid E. (2012) Tissue factor in blood cells and endothelial cells. Front. Biosci. (Elite Ed.), 4, 289-299. CrossRef Scholar google search
