Protective and Indicating Effect of Indirect Bilirubin in Intracranial or Extracranial Artery Atherosclerotic Stenosis Progresses — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Protective and Indicating Effect of Indirect Bilirubin in Intracranial or Extracranial Artery Atherosclerotic Stenosis Progresses
Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
,
Department of Neurology, Yancheng Third People’s Hospital, Yancheng, China
,
Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
,
Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
,
Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
,
Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
1 Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
2 Department of Neurology, Yancheng Third People’s Hospital, Yancheng, China
3 Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
4 Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
5 Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
6 Department of Neurology, Clinical Medical College, Yangzhou University, Yangzhou, China
Background : Bilirubin is the metabolic end-product of heme degradation by heme oxy-genase (HO), which has recently been shown to act as an antioxidant which can protect against atherosclerosis. This study explored the relationship between serum bilirubin levels and different degrees of atherosclerotic stenosis in intracranial or extracranial arteries. Methods : The study included 189 patients undergoing digital subtraction angiography (DSA) diagnosed as being normal or having been confirmed as atherosc lerotic stenosis in the intracranial or extracranial arteries. The patients were allocated to normal, mild (<50% diameter stenosis), moderate (50% - 69% stenosis), severe (70% - 99% stenosis) and occlusion groups according to the severity of stenosis proved by DSA. Blood samples were collected to determine bilirubin concentrations and other biochemical indicators of atherosclerosis. Univariate and multivariate analyses were performed to evaluate the associations between disease severity and biomarkers. Results : Indirect bilirubin (Ibil) concentrations increased in parallel with the increasing severity of atherosclerotic stenosis in the intracranial or extracranial arteries, but decreased in patients with occluded cranial vessels. Multivariate analysis showed that Ibil levels were significantly higher in patients with severe stenosis group than in those with mild stenosis (OR, 1.464; 95% CI, 1.050 - 2.042; P = 0.024). However, Ibil levels were significantly lower in patients with occlusion than in those with severe stenosis (OR, 0.790; 95% CI, 0.684 - 0.913; P = 0.001). Conclusions : Ibil appears to have a protective effect against the development of atherosclerotic stenosis in intracranial or extracranial arteries. The biosynthesis of Ibil increases with stenosis progresses but decreases once occlusion occurs.
Bonati, L.H., Dobson, J., Featherstone, R.L., Ederle, J., van der Worp, H.B., de Borst, G.J., Mali, W.P.T.M., Beard, J.D., Cleveland, T., Engelter, S.T., Lyrer, P.A., Ford, G.A., Dorman, P.J. and Brown, M.M. (2015) Long-Term Outcomes after Stenting Versus Endarterectomy for Treatment of Symptomatic Carotid Stenosis: The International Carotid Stenting Study (ICSS) Randomised Trial. The Lancet, 385, 529-538. http://dx.doi.org/10.1016/S0140-6736(14)61184-3
Ma, N., Xu, Z., Mo, D., Gao, F., Gao, K., Sun, X., Xu, X., Liu, L., Song, L., Wang, T., Zhao, X., Wang, Y., Wang, Y. and Miao, Z. (2014) Safety of Low-Dose Aspirin in Endovascular Treatment for Intracranial Atherosclerotic Stenosis. PloS One, 9, e105252. http://dx.doi.org/10.1371/journal.pone.0105252
Kern, R., Steinke, W., Daffertshofer, M., Prager, R. and Hennerici, M. (2005) Stroke Recurrences in Patients with Symptomatic vs Asymptomatic Middle Cerebral Artery Disease. Neurology, 65, 859-864. http://dx.doi.org/10.1212/01.wnl.0000175983.76110.59
Tegos, T.J., Kalodiki, E., Daskalopoulou, S.S. and Nicolaides, A.N. (2000) Stroke: Epidemiology, Clinical Picture, and Risk Factors—Part I of III. Angiology, 51, 793-808. http://dx.doi.org/10.1177/000331970005101001
Qian, Y., Pu, Y., Liu, L., Wang, D.Z., Zhao, X., Wang, C., Wang, Y., Liu, G., Pan, Y. and Wang, Y. (2013) Low HDL-C Level Is Associated with the Development of Intracranial Artery Stenosis: Analysis from the Chinese IntraCranial Athero Sclerosis (CICAS) Study. PloS One, 8, e64395. http://dx.doi.org/10.1371/journal.pone.0064395
Erkan, A., Ekici, B., Ugurlu, M., Is, G., Seker, R., Demirtas, S. and Korkmaz, S. (2014) The Role of Bilirubin and Its Protective Function against Coronary Heart Disease. Herz, 39, 711-715. http://dx.doi.org/10.1007/s00059-013-3872-5
Giraudi, P.J., Bellarosa, C., Coda-Zabetta, C.D., Peruzzo, P. and Tiribelli, C. (2011) Functional Induction of the Cystine-Glutamate Exchanger System Xc(-) Activity in SH-SY5Y Cells by Unconjugated Bilirubin. PloS One, 6, e29078. http://dx.doi.org/10.1371/journal.pone.0029078
Huang, S.S., Huang, P.H., Wu, T.C., Chen, J.W. and Lin, S.J. (2012) Association of Serum Bilirubin with Contrast-Induced Nephropathy and Future Cardiovascular Events in Patients Undergoing Coronary Intervention. PloS One, 7, e42594. http://dx.doi.org/10.1371/journal.pone.0042594
Deetman, P.E., Bakker, S.J., Kwakernaak, A.J., Navis, G. and Dullaart, R.P. (2014) The Relationship of the Anti-Oxidant Bilirubin with Free Thyroxine Is Modified by Insulin Resistance in Euthyroid Subjects. PloS One, 9, e90886. http://dx.doi.org/10.1371/journal.pone.0090886
Erdogan, D., Gullu, H., Yildirim, E., Tok, D., Kirbas, I., Ciftci, O., Baycan, S.T. and Muderrisoglu, H. (2006) Low Serum Bilirubin Levels Are Independently and Inversely Related to Impaired Flow-Mediated Vasodilation and Increased Carotid Intima-Media Thickness in Both Men and Women. Atherosclerosis, 184, 431-437. http://dx.doi.org/10.1016/j.atherosclerosis.2005.05.011
Akboga, M.K., Canpolat, U., Sahinarslan, A., Alsancak, Y., Nurkoc, S., Aras, D., Aydogdu, S. and Abaci, A. (2015) Association of Serum Total Bilirubin Level with Severity of Coronary Atherosclerosis Is Linked to Systemic Inflammation. Atheroscleosis, 240, 110-114. http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.051
Ryu, S., Chang, Y., Zhang, Y., Woo, H.Y., Kwon, M.J., Park, H., Lee, K.B., Son, H.J., Cho, J. and Guallar, E. (2014) Higher Serum Direct Bilirubin Levels Were Associated with a Lower Risk of Incident Chronic Kidney Disease in Middle Aged Korean Men. PloS One, 9, e75178. http://dx.doi.org/10.1371/journal.pone.0075178
Schwertner, H.A., Jackson, W.G. and Tolan, G. (1994) Association of Low Serum Concentration of Bilirubin with Increased Risk of Coronary Artery Disease. Clinical Chemistry, 40, 18-23.
Ishizaka, N., Ishizaka, Y., Takahashi, E., Yamakado, M. and Hashimoto, H. (2001) High Serum Bilirubin Level Is Inversely Associated with the Presence of Carotid Plaque. Stroke: A Journal of Cerebral Circulation, 32, 580-583. http://dx.doi.org/10.1161/01.STR.32.2.580-b
Perlstein, T.S., Pande, R.L., Beckman, J.A. and Creager, M.A. (2008) Serum Total Bilirubin Level and Prevalent Lower-Extremity Peripheral Arterial Disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 166-172. http://dx.doi.org/10.1161/ATVBAHA.107.153262
Kimm, H., Yun, J.E., Jo, J. and Jee, S.H. (2009) Low Serum Bilirubin Level as an Independent Predictor of Stroke Incidence: A Prospective Study in Korean Men and Women. Stroke: A Journal of Cerebral Circulation, 40, 3422-3427. http://dx.doi.org/10.1161/STROKEAHA.109.560649
Kuwano, T., Miura, S., Shirai, K., Ike, A., Mori, K., Shimizu, T., Zhang, B., Iwata, A., Nishikawa, H., Kawamura, A. and Saku, K. (2011) Serum Levels of Bilirubin as an Independent Predictor of Coronary In-Stent Restenosis: A New Look at an Old Molecule. Journal of Atherosclerosis and Thrombosis, 18, 574-583. http://dx.doi.org/10.5551/jat.6643
Rothwell, P.M., Gutnikov, S.A. and Warlow, C.P. (2003) Reanalysis of the Final Results of the European Carotid Surgery Trial. Stroke: A Journal of Cerebral Circulation, 34, 514-523. http://dx.doi.org/10.1161/01.STR.0000054671.71777.C7
Li, S., Guo, Y.L., Xu, R.X., Zhang, Y., Zhu, C.G., Sun, J., Qing, P., Wu, N.Q., Jiang, L.X. and Li, J.J. (2014) Association of Plasma PCSK9 Levels with White Blood Cell Count and Its Subsets in Patients with Stable Coronary Artery Disease. Atherosclerosis, 234, 441-445. http://dx.doi.org/10.1016/j.atherosclerosis.2014.04.001
Ishizaka, N., Ishizaka, Y., Toda, E., Nagai, R. and Yamakado, M. (2005) Association between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 1038-1044. http://dx.doi.org/10.1161/01.ATV.0000161274.87407.26
Neuzil, J. and Stocker, R. (1994) Free and Albumin-Bound Bilirubin Are Efficient Co-Antioxidants for Alpha-Tocopherol, Inhibiting Plasma and Low Density Lipoprotein Lipid Peroxidation. The Journal of Biological Chemistry, 269, 16712-16719.
Nakayama, M., Takahashi, K., Komaru, T., Fukuchi, M., Shioiri, H., Sato, K., Kitamuro, T., Shirato, K., Yamaguchi, T., Suematsu, M. and Shibahara, S. (2001) Increased Expression of Heme Oxygenase-1 and Bilirubin Accumulation in Foam Cells of Rabbit Atherosclerotic Lesions. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 1373-1377. http://dx.doi.org/10.1161/hq0801.093592
Ollinger, R., Yamashita, K., Bilban, M., Erat, A., Kogler, P., Thomas, M., Csizmadia, E., Usheva, A., Margreiter, R. and Bach, F.H. (2007) Bilirubin and Biliverdin Treatment of Atherosclerotic Diseases. Cell Cycle, 6, 39-43. http://dx.doi.org/10.4161/cc.6.1.3700
Vitek, L. and Schwertner, H.A. (2007) The Heme Catabolic Pathway and Its Protective Effects on Oxidative Stress-Mediated Diseases. Advances in Clinical Chemistry, 43, 1-57. http://dx.doi.org/10.1016/S0065-2423(06)43001-8
Ollinger, R., Bilban, M., Erat, A., Froio, A., McDaid, J., Tyagi, S., Csizmadia, E., Graca-Souza, A.V., Liloia, A., Soares, M.P., Otterbein, L.E., Usheva, A., Yamashita, K. and Bach, F.H. (2005) Bilirubin: A Natural Inhibitor of Vascular Smooth Muscle Cell Proliferation. Circulation, 112, 1030-1039. http://dx.doi.org/10.1161/CIRCULATIONAHA.104.528802
Peyton, K.J., Shebib, A.R., Azam, M.A., Liu, X.M., Tulis, D.A. and Durante, W. (2012) Bilirubin Inhibits Neointima Formation and Vascular Smooth Muscle Cell Proliferation and Migration. Frontiers in Pharmacology, 3, 48. http://dx.doi.org/10.3389/fphar.2012.00048
Yang, X.F., Chen, Y.Z., Su, J.L., Wang, F.Y. and Wang, L.X. (2009) Relationship between Serum Bilirubin and Carotid Atherosclerosis in Hypertensive Patients. Internal Medicine, 48, 1595-1599. http://dx.doi.org/10.2169/internalmedicine.48.2286
Stocker, R., Yamamoto, Y., McDonagh, A.F., Glazer, A.N. and Ames, B.N. (1987) Bilirubin Is an Antioxidant of Possible Physiological Importance. Science, 235, 1043-1046. http://dx.doi.org/10.1126/science.3029864
Frei, B., Stocker, R. and Ames, B.N. (1988) Antioxidant Defenses and Lipid Peroxidation in Human Blood Plasma. Proceedings of the National Academy of Sciences of the United States of America, 85, 9748-9752. http://dx.doi.org/10.1073/pnas.85.24.9748
Yamaguchi, T., Terakado, M., Horio, F., Aoki, K., Tanaka, M. and Nakajima, H. (1996) Role of Bilirubin as an Antioxidant in an Ischemia-Reperfusion of Rat Liver and Induction of Heme Oxygenase. Biochemical and Biophysical Research Communications, 223, 129-135. http://dx.doi.org/10.1006/bbrc.1996.0857
Trappolini, M., Stoppo, M., Meggiorini, M., Loguercio, V., Fabiani, O., Iannotta, M., Negro, A., Sebastianelli, A., Proietta, M., Del Porto, F. and Aliberti, G. (2009) The Plasma Fibrinogen as a Marker of Subclinical Carotid Atherosclerosis. Recenti Progressi in Medicina, 100, 352-355.
Redgrave, J.N., Lovett, J.K. and Rothwell, P.M. (2010) Histological Features of Symptomatic Carotid Plaques in Relation to Age and Smoking: The Oxford Plaque Study. Stroke: A Journal of Cerebral Circulation, 41, 2288-2294. http://dx.doi.org/10.1161/STROKEAHA.110.587006