Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 5, May, p. 683–692
Publication type: original article
Chronic and oxidative stress association with total count of endothelial microvesicles in healthy young male plasma
1 Departament of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Biomedicine Institute, Faculty of Medicine, Vilnius University, Lithuania
2 Center for Laboratory Medicine, Vilnius University Hospital Santaros Clinics, Lithuania
Background. Chronic and oxidative stress promotes injury to the endothelium. This happens early in the disease and novel biomarkers describing the rate of the damage may be important in early diagnostics and prevention. Microvesicles are shed from endothelial cells in response to oxidative stress, inflammation, coagulation, and angiogenesis. Their increased level in plasma could reflect the state of the endothelium.
Objectives. The objective of this study was to test the association between oxidative and chronic stress markers, atherosclerosis risk factors and endothelial microvesicle (EMV) count in peripheral blood.
Material and Methods. The study included 81 males, aged 25–55 years and apparently healthy. Venous blood samples were labeled with anti-CD144-FITC, anti-CD105-BV421, anti-CD42a-PerCP, anti-CD62e-PE, anti-CD31-APCy7, and anti-CD61-APC (BD Biosciences, San Jose, USA), and tested using a BD LSR Fortessa cytometer (BD Biosciences). Events were gated on forward and side-scattered light parameters. Malondialdehyde (MDA) and cortisol concentrations were measured using high-performance liquid chromatography (HPLC).
Results. Four populations of EMV expressing a combination of CD105+, CD31+, CD144+, and CD62e with CD42aor CD42a+ markers were examined. We found correlations between MDA concentration and hair cortisol and a total count of CD144+ microvesicles, and weak correlations with diastolic blood pressure (DBP) (p = 0.003, r = 0.324) and systolic blood pressure (SBP) (p = 0.016, r = 0.267), especially with the microvesicles carrying CD62e. There was a median difference of CD105+ microvesicle count between smoking (n = 13) and non-smoking (n = 68) individuals. A predictive model showed an association between CD144+ microvesicle counts with cortisol and MDA concentrations and waist circumference.
Conclusion. In conclusion, our data and predictive model showed that the total counts of microvesicle populations were associated with stress-related parameters – cortisol and MDA concentrations; expression of CD62e in various populations of EMV and the ratio of CD144+ to CD105+/CD62e+ were associated with increased DBP and SBP, and also with total cholesterol concentration in healthy young male population.
flow cytometry, oxidative stress, atherosclerosis, dyslipidemia, microvesicles
- Stocker R, Keaney JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–1478.
- Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126–1167.
- Matsuzawa Y, Lerman A. Endothelial dysfunction and coronary artery disease: Assessment, prognosis, and treatment. Coron Artery Dis. 2014;25(8):713–724.
- Lee R, Margaritis M, Channon K, Antoniades C. Evaluating oxidative stress in human cardiovascular disease: Methodological aspects and consid-erations. Curr Med Chem. 2012;19(16):2504–2520.
- Mastromonaco GF, Gunn K, McCurdy-Adams H, Edwards DB, Schulte-Hostedde AI. Validation and use of hair cortisol as a measure of chronic stress in eastern chipmunks (Tamias striatus). Conserv Physiol. 2014;2(1):cou055.
- Schiro A, Wilkinson FL, Weston R, Smyth JV, Serracino-Inglott F, Alexander MY. Endothelial microparticles as conveyors of information in atherosclerotic disease. Atherosclerosis. 2014;234(2):295–302.
- Paudel KR, Panth N, Kim D-W. Circulating endothelial microparticles: A key hallmark of atherosclerosis progression. Scientifica (Cairo). 2016;2016:8514056.
- Barteneva NS, Fasler-Kan E, Bernimoulin M, et al. Circulating microparticles: Square the circle. BMC Cell Biol. 2013;14:23.
- Fairweather DL. Sex differences in inflammation during atherosclerosis. Clin Med Insights Cardiol. 2014;8(Suppl 3):49–59.
- Khoschsorur GA, Winklhofer-Roob BM, Rabl H, et al. Evaluation of a sensitive HPLC method for the determination of malondialdehyde, and applica-tion of the method to different biological materials. Chromatographia. 2000;52(3):181.
- Raul JS, Cirimele V, Ludes B, Kintz P. Detection of physiological concentrations of cortisol and cortisone in human hair. Clin Biochem. 2004;37(12):1105–1111.
- De Palo EF, Antonelli G, Benetazzo A, Prearo M, Gatti R. Human saliva cortisone and cortisol simultaneous analysis using reverse phase HPLC technique. Clin Chim Acta. 2009;405(1–2):60–65.
- Jin Z-G, Lungu AO, Xie L, Wang M, Wong C, Berk BC. Cyclophilin A is a proinflammatory cytokine that activates endothelial cells. Arterioscler Thromb Vasc Biol. 2004;24(7):1186–1191.
- 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.
- Colombo E, Borgiani B, Verderio C, Furlan R. Microvesicles: Novel biomarkers for neurological disorders. Front Physiol. 2012;3:63.
- Nozaki T, Sugiyama S, Koga H, 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(7):601–608.
- Preston RA, Jy W, Jimenez JJ, et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003;41(2):211–217.
- Li P, Qin C. Elevated circulating VE-cadherin + CD144 + endothelial microparticles in ischemic cerebrovascular disease. Thromb Res. 2015;135(2):375–381.
- Trappenburg MC, van Schilfgaarde M, Marchetti M, et al. Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia. Haematologica. 2009;94(7):911–918.
- Eldh M, Ekström K, Valadi H, et al. Exosomes communicate protective messages during oxidative stress: Possible role of exosomal shuttle RNA. PLoS One. 2010;5(12):e15353.
- Ren S, Fan X, Peng L, et al. Expression of NF-κB, CD68 and CD105 in carotid atherosclerotic plaque. J Thorac Dis. 2013;5(6):771–776.
- Li C, Mollahan P, Baguneid MS, et al. Comparative study of neovascularization in atherosclerotic plaques using CD31, CD105 and TGFβ1. Patho-biology. 2006;73(4):192–197.
- Mobarrez F, Antoniewicz L, Bosson JA, Kuhl J, Pisetsky DS, Lundbäck M. The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers. PLoS One. 2014;9(2):e90314.
- 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.
- Kjærgaard AG, Dige A, Krog J, Tønnesen E, Wogensen L. Soluble adhesion molecules correlate with surface expression in an in vitro model of endothelial activation. Basic Clin Pharmacol Toxicol. 2013;113(4):273–279.
- Werner N, Wassmann S, Ahlers P, Kosiol S, Nickenig G. Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2006;26(1):112–116.