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1
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA 98103-7110.
a Address for correspondence: Department of Clinical Biochemistry, Hadassah Medical Center and Hebrew University–Hadassah Medical School, PO Box 12000, Jerusalem, Israel 91120. Fax 972-2-6435778; e-mail mayer{at}hadassah.org.il
Background: Lipid oxidation and formation of oxygen radicals are important elements of arterial plaque formation and atherosclerosis, and are involved in the pathophysiology of coronary artery disease (CAD). Because bilirubin has antioxidant properties, it has been suggested that it may have a protective role in the atherosclerotic process.
Approach: This review examines in vitro and in vivo studies indicating that bilirubin inhibits lipid oxidation and oxygen radical formation. Experimental and epidemiological evidence is presented that suggests that bilirubin may serve as a physiological antioxidant providing protection against atherosclerosis and CAD. Special attention is focused on studies that noted an inverse relationship between plasma bilirubin concentration and cardiovascular morbidity.
Content: Serum bilirubin concentrations in the upper portion of the reference interval reportedly reduce atherogenic risk and provide protection against CAD. In contrast, serum bilirubin concentrations in the lower portion of the reference interval may be associated with increased risk of ischemic heart disease.
Summary: Taken together, the evidence presented in this review supports the concept that bilirubin, via its antioxidant potential, has antiatherogenic properties and that an inverse relationship exists between circulating bilirubin concentrations and risk of CAD.
The following articles in journals at HighWire Press have cited this article:
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 H. Schroder No Nitric Oxide for HO-1 from Sodium Nitroprusside Mol. Pharmacol., May 1, 2006; 69(5): 1507 - 1509. [Abstract] [Full Text] [PDF]
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T. Morita Heme Oxygenase and Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1786 - 1795. [Abstract] [Full Text] [PDF]
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 A Granato, G Gores, M T Vilei, R Tolando, C Ferraresso, and M Muraca Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes Gut, December 1, 2003; 52(12): 1774 - 1778. [Abstract] [Full Text] [PDF]
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 P. J. Bosma, I. M. van der Meer, C. T. Bakker, A. Hofman, M. Paul-Abrahamse, and J. C. Witteman UGT1A1*28 Allele and Coronary Heart Disease: The Rotterdam Study Clin. Chem., July 1, 2003; 49(7): 1180 - 1181. [Full Text] [PDF]
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G. Endler, A. Hamwi, R. Sunder-Plassmann, M. Exner, T. Vukovich, C. Mannhalter, J. Wojta, K. Huber, and O. Wagner Is Low Serum Bilirubin an Independent Risk Factor for Coronary Artery Disease in Men but Not in Women? Clin. Chem., July 1, 2003; 49(7): 1201 - 1204. [Full Text] [PDF]
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 S. Oberle, A. Abate, N. Grosser, A. Hemmerle, H. J. Vreman, P. A. Dennery, H. T. Schneider, D. Stalleicken, and H. Schroder Endothelial Protection by Pentaerithrityl Trinitrate: Bilirubin and Carbon Monoxide as Possible Mediators Experimental Biology and Medicine, May 1, 2003; 228(5): 529 - 534. [Abstract] [Full Text] [PDF]
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S. Ching, D. Ingram, R. Hahnel, J. Beilby, and E. Rossi Serum Levels of Micronutrients, Antioxidants and Total Antioxidant Status Predict Risk of Breast Cancer in a Case Control Study J. Nutr., February 1, 2002; 132(2): 303 - 306. [Abstract] [Full Text] [PDF]
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