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Cholesterol  2014 

Association of the Total Cholesterol Content of Erythrocyte Membranes with the Severity of Disease in Stable Coronary Artery Disease

DOI: 10.1155/2014/821686

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Increasing evidence suggests that erythrocytes may participate in atherogenesis. We sought to investigate whether the total cholesterol content of erythrocyte membranes (CEM) is significantly different in patients with stable coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between CEM and the severity of coronary stenosis. Methods. The population included 144 patients, undergoing clinically indicated coronary angiography. The severity of coronary stenosis was scored after coronary angiography and patients were divided into two groups; the -stenosis group (CAD patients, ) had a significant stenosis indicated by coronary angiography and the second group, -stenosis (), had nonsignificant coronary stenosis. Lipid parameters were determined by routine laboratory methods. CEM was measured using an enzymatic assay, and protein content was assessed by the modified Lowry method. Results. The mean of CEM levels was higher () in stable CAD patients (137.2?μg/mg of membrane protein) compared with -stenosis patients (110.0?μg/mg of membrane protein). The coronary artery scores were correlated positively with CEM levels (, ). Conclusion. CEM levels are positively associated with the severity of CAD, meaning that CEM might contribute to the development of CAD. 1. Introduction Coronary artery disease (CAD) is closely associated with advanced atherosclerosis, which reflects several deteriorative phenomena that gradually result in narrowing of coronary arteries, terminating in thrombosis and myocardial infarction. CAD is one of the major causes of mortality and morbidity in both developed and developing countries and is believed to have a multifactorial etiology, composed of numerous biological, environmental, behavioral, and sociocultural factors [1–3]. In addition to traditional risk factors, erythrocyte membrane has been regarded as one of the most important contributors to the initiation and progression of atherosclerosis [4–11]. Although apoptotic macrophages are an important source of cholesterol within atherosclerotic plaques, it is unlikely that all of the cholesterol contained in plaques derives from foam cells alone. Most of the cholesterol in foam cell is esterified [12], whereas the atherosclerotic lipid core has a remarkably high content of free cholesterol [13]. The most compelling evidence was reported by Arbustini et al. [14], who identified an erythrocyte membrane protein, glycophorin A, in pulmonary plaques from patients with thromboembolic disease. These findings were repeated in


[1]  G. K. Hansson, “Inflammation, atherosclerosis, and coronary artery disease,” The New England Journal of Medicine, vol. 352, no. 16, pp. 1626–1695, 2005.
[2]  R. Stocker and J. Keaney, “Role of oxidative modifications in atherosclerosis,” Physiological Reviews, vol. 84, no. 4, pp. 1381–1478, 2004.
[3]  P. Libby, M. Aikawa, and U. Sch?nbeck, “Cholesterol and atherosclerosis,” Biochimica et Biophysica Acta—Molecular and Cell Biology of Lipids, vol. 1529, no. 1–3, pp. 299–309, 2000.
[4]  W. E. Hellings, W. Peeters, F. L. Moll, and G. Pasterkamp, “From vulnerable plaque to vulnerable patient: the search for biomarkers of plaque destabilization,” Trends in Cardiovascular Medicine, vol. 17, no. 5, pp. 162–171, 2007.
[5]  D. N. Tziakas, G. K. Chalikias, D. Stakos, and H. Boudoulas, “The role of red blood cells in the progression and instability of atherosclerotic plaque,” International Journal of Cardiology, vol. 142, no. 1, pp. 2–7, 2010.
[6]  D. N. Tziakas, G. K. Chalikias, D. Stakos et al., “Independent and additive predictive value of total cholesterol content of erythrocyte membranes with regard to coronary artery disease clinical presentation,” International Journal of Cardiology, vol. 150, no. 1, pp. 22–27, 2011.
[7]  J. Zhang, L. Pan, Y. Xu et al., “Total cholesterol content of erythrocyte membranes in acute coronary syndrome: correlation with apolipoprotein A-I and lipoprotein (a),” Coronary Artery Disease, vol. 22, no. 3, pp. 145–152, 2011.
[8]  K. C. Koskinas and G. D. Giannoglou, “Intraplaque hemorrhage, RBC-derived cholesterol, and plaque progression: time to move from conjecture to evidence?” JACC: Cardiovascular Imaging, vol. 5, no. 11, pp. 1185–1186, 2012.
[9]  D. Tziakas, G. Chalikias, A. Grapsa, T. Gioka, I. Tentes, and S. Konstantinides, “Red blood cell distribution width—a strong prognostic marker in cardiovascular disease—is associated with cholesterol content of erythrocyte membrane,” Clinical Hemorheology and Microcirculation, vol. 51, no. 4, pp. 243–254, 2012.
[10]  Y. Zhong, H. Tang, Q. Zeng et al., “Total cholesterol content of erythrocyte membranes is associated with the severity of coronary artery disease and the therapeutic effect of rosuvastatin,” Upsala Journal of Medical Sciences, vol. 117, no. 4, pp. 390–398, 2012.
[11]  J. Zhang, K. Tu, Y. Xu, et al., “Sphingomyelin in erythrocyte membranes increases the total cholesterol content of erythrocyte membranes in patients with acute coronary syndrome,” Coronary Artery Disease, vol. 24, no. 5, pp. 361–367, 2013.
[12]  I. Tabas, “Cholesterol and phospholipid metabolism in macrophages,” Biochimica et Biophysica Acta, vol. 1529, no. 1–3, pp. 164–174, 2000.
[13]  J. R. Guyton and K. F. Klemp, “Development of the lipid-rich core in human atherosclerosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 16, no. 1, pp. 4–11, 1996.
[14]  E. Arbustini, P. Morbini, A. M. D'Armini et al., “Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation,” Heart, vol. 88, no. 2, pp. 177–182, 2002.
[15]  F. D. Kolodgie, H. K. Gold, A. P. Burke, et al., “Intraplaque hemorrhage and progression of coronary atheroma,” The New England Journal of Medicine, vol. 349, no. 24, pp. 2316–2325, 2003.
[16]  D. N. Tziakas, J. C. Kaski, G. K. Chalikias et al., “Total cholesterol content of erythrocyte membranes is increased in patients with acute coronary syndrome: a new marker of clinical instability?” Journal of the American College of Cardiology, vol. 49, no. 21, pp. 2081–2089, 2007.
[17]  R. Virmani, F. D. Kolodgie, A. P. Burke et al., “Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 10, pp. 2054–2061, 2005.
[18]  A. Emami Razavi, M. Pourfarzam, M. Ani, and G. A. Naderi, “The associations between high-density lipoprotein mean particle size and its fatty acid composition,” Biomarkers in Medicine, vol. 7, no. 2, pp. 235–245, 2013.
[19]  M. Siavash, M. Sadeghi, F. Salarifar, M. Amini, and F. Shojaee-Moradie, “Comparison of body mass index and waist/height ratio in predicting definite coronary artery disease,” Annals of Nutrition and Metabolism, vol. 53, no. 3-4, pp. 162–166, 2009.
[20]  V. Chauhan, J. Tsiouris, A. Chauhan, A. M. Sheikh, W. T. Brown, and M. Vaughan, “Increased oxidative stress and decreased activities of Ca2+/Mg2+-ATPase and Na+/K+-ATPase in the red blood cells of the hibernating black bear,” Life Sciences, vol. 71, no. 2, pp. 153–161, 2002.
[21]  M. DeLuise and J. S. Flier, “Functionally abnormal Na+-K+ pump in erythrocytes of a morbidly obese patient,” The Journal of Clinical Investigation, vol. 69, no. 1, pp. 38–44, 1982.
[22]  M. A. K. Markwell, S. M. Haas, L. L. Bieber, and N. E. Tolbert, “A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples,” Analytical Biochemistry, vol. 87, no. 1, pp. 206–210, 1978.
[23]  J. Folch, M. Lees, and G. H. Sloane Stanley, “A simple method for the isolation and purification of total lipides from animal tissues,” The Journal of biological chemistry, vol. 226, no. 1, pp. 497–509, 1957.
[24]  G. D. Giannoglou, K. C. Koskinas, D. N. Tziakas et al., “Total cholesterol content of erythrocyte membranes and coronary atherosclerosis: an intravascular ultrasound pilot study.,” Angiology, vol. 60, no. 6, pp. 676–682, 2009.
[25]  M.-M. Yu, Y. Xu, J.-H. Zhang, et al., “Total cholesterol content of erythrocyte membranes levels are associated with the presence of acute coronary syndrome and high sensitivity C-reactive protein,” International Journal of Cardiology, vol. 145, no. 1, pp. 57–58, 2010.
[26]  M. H. Gottlieb, “Rates of cholesterol exchange between human erythrocytes and plasma lipoproteins,” Biochimica et Biophysica Acta, vol. 600, no. 2, pp. 530–541, 1980.
[27]  C. J. Fielding and P. E. Fielding, “Intracellular cholesterol transport,” Journal of Lipid Research, vol. 38, no. 8, pp. 1503–1521, 1997.


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