Haemeoxygenase signalling pathway: Implications for cardiovascular disease

European Heart Journal

Volumn 36, Issue 24, 2015, Pages 1512-1518

  Fredenburgh, Laura E ^a   Merz, Allison A ^a   Cheng, Susan ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b FRAMINGHAM HEART STUDY   (United States)

Author keywords

Bilirubin; Biliverdin; Carbon monoxide; Cardiovascular disease; Heme oxygenase pathway

Indexed keywords

HEME; HEME OXYGENASE; ANTIOXIDANT; AUTACOID;

ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CELL PROLIFERATION; ENVIRONMENTAL FACTOR; ENZYME ACTIVITY; ENZYME METABOLISM; ENZYME REGULATION; GENETIC TRAIT; HUMAN; META ANALYSIS (TOPIC); NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; CARDIOVASCULAR DISEASES; ENZYMOLOGY; FORECASTING; GENE EXPRESSION; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; RISK FACTOR; THROMBOCYTE AGGREGATION; THROMBOSIS; VASOCONSTRICTION; VASODILATATION;

ANTIOXIDANTS; APOPTOSIS; CARDIOVASCULAR DISEASES; CELL PROLIFERATION; FORECASTING; GENE EXPRESSION; HEME; HEME OXYGENASE (DECYCLIZING); HUMANS; INFLAMMATION MEDIATORS; PLATELET AGGREGATION; RISK FACTORS; SIGNAL TRANSDUCTION; THROMBOSIS; VASOCONSTRICTION; VASODILATION;

EID: 84942417144     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv114     Document Type: Review

References (193)

1. Nath KA, Balla G, Vercellotti GM, Balla J, Jacob HS, Levitt MD, Rosenberg ME. Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 1992;90:267-270.
2. Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM. Ferritin: A cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992; 267:18148-18153.
3. Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 1999;103:129-135.
4. Song J, Sumiyoshi S, Nakashima Y, Doi Y, Iida M, Kiyohara Y, Sueishi K. Overexpression of heme oxygenase-1 in coronary atherosclerosis of Japanese autopsies with diabetes mellitus: Hisayama study. Atherosclerosis 2009;202:573-581.
5. Jeney V, Balla J, Yachie A, Varga Z, Vercellotti GM, Eaton JW, Balla G. Pro-oxidant and cytotoxic effects of circulating heme. Blood 2002;100:879-887.
6. Fredenburgh LE, Perrella MA, Mitsialis SA. The role of heme oxygenase-1 in pulmonary disease. Am J Respir Cell Mol Biol 2007;36:158-165.
7. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science 1987;235:1043-1046.
8. Sarady-Andrews JK, Liu F, Gallo D, Nakao A, Overhaus M, Ollinger R, Choi AM, Otterbein LE. Biliverdin administration protects against endotoxin-induced acute lung injury in rats. Am J Physiol Lung Cell Mol Physiol 2005;289:L1131-L1137.
9. Choi BM, Pae HO, Jeong YR, Oh GS, Jun CD, Kim BR, Kim YM, Chung HT. Overexpression of heme oxygenase (HO)-1 renders Jurkat T cells resistant to fasmediated apoptosis: involvement of iron released by HO-1. Free Radic Biol Med 2004;36:858-871.
10. Otterbein LE, Mantell LL, Choi AM. Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol 1999;276:L688-L694.
11. Otterbein LE, Otterbein SL, Ifedigbo E, Liu F, Morse DE, Fearns C, Ulevitch RJ, Knickelbein R, Flavell RA, Choi AM. MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J Pathol 2003;163:2555-2563.
12. Otterbein LE, Choi AM. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 2000;279:L1029-L1037.
13. Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM. Carbon monoxide has anti-inflammatory effects involving the mitogenactivated protein kinase pathway. Nat Med 2000;6:422-428.
14. Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AM, Soares MP. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 2000;192:1015-1026.
15. Zhang X, Shan P, Alam J, Davis RJ, Flavell RA, Lee PJ. Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogenactivated protein kinase pathway during ischemia-reperfusion lung injury. J Biol Chem 2003;278:22061-22070.
16. Song R, Mahidhara RS, Liu F, NingW, Otterbein LE, Choi AM. Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen-activated protein kinase pathway. Am J Respir Cell Mol Biol 2002;27:603-610.
17. Zhou Z, Song R, Fattman CL, Greenhill S, Alber S, Oury TD, Choi AM, Morse D. Carbon monoxide suppresses bleomycin-induced lung fibrosis. Am J Pathol 2005; 166:27-37.
18. Fujita T, Toda K, Karimova A, Yan SF, Naka Y, Yet SF, Pinsky DJ. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 2001;7:598-604.
19. Morita T, Mitsialis SA, Koike H, Liu Y, Kourembanas S. Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells. J Biol Chem 1997;272: 32804-32809.
20. Brune B, Ullrich V. Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 1987;32:497-504.
21. Morita T, Perrella MA, Lee ME, Kourembanas S. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci USA 1995; 92:1475-1479.
22. Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 1968;61:748-755.
23. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006;86:583-650.
24. Kronke G, BochkovVN, Huber J, Gruber F, Bluml S, Furnkranz A, Kadl A, Binder BR, Leitinger N. Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein. J Biol Chem 2003;278:51006-51014.
25. Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, ClintonWebb R, Lee ME, Nabel GJ, Nabel EG. Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 2001;7:693-698.
26. Chen XL, Varner SE, Rao AS, Grey JY, Thomas S, Cook CK, Wasserman MA, Medford RM, Jaiswal AK, Kunsch C. Laminar flowinduction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism. J Biol Chem 2003;278:703-711.
27. Hamdulay SS, Wang B, Birdsey GM, Ali F, Dumont O, Evans PC, Haskard DO, Wheeler-Jones CP, Mason JC. Celecoxib activates PI-3 K/Akt and mitochondrial redox signaling to enhance heme oxygenase-1-mediated anti-inflammatory activity in vascular endothelium. Free Radic Biol Med 2010;48:1013-1023.
28. 2+, and phospholipase A2 in endothelial cells. Am J Physiol 1999;276:H1493-H1501.
29. Sun J, Brand M, Zenke Y, Tashiro S, Groudine M, Igarashi K. Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network. Proc Natl Acad Sci USA 2004;101:1461-1466.
30. Omura S, Suzuki H, Toyofuku M, Ozono R, Kohno N, Igarashi K. Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury. Genes Cells 2005;10:277-285.
31. Watari Y, Yamamoto Y, Brydun A, Ishida T, Mito S, Yoshizumi M, Igarashi K, Chayama K, Ohshima T, Ozono R. Ablation of the bach1 gene leads to the suppression of atherosclerosis in bach1 and apolipoprotein E double knockout mice. Hypertens Res 2008;31:783-792.
32. Chen J, Zhang Z, Cai L. Diabetic cardiomyopathy and its prevention by nrf2: current status. Diabetes Metab J 2014;38:337-345.
33. Kondo K, Ishigaki Y, Gao J, Yamada T, Imai J, Sawada S, Muto A, Oka Y, Igarashi K, Katagiri H. Bach1 deficiency protects pancreatic beta-cells from oxidative stress injury. Am J Physiol Endocrinol Metab 2013;305:E641-E648.
34. Yano Y, Ozono R, Oishi Y, Kambe M, Yoshizumi M, Ishida T, Omura S, Oshima T, Igarashi K. Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice. Genes Cells 2006;11:791-803.
35. Velmurugan GV, Sundaresan NR, Gupta MP, White C. Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes. Cardiovasc Res 2013;100:143-150.
36. He X, Kan H, Cai L, Ma Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 2009;46:47-58.
37. Mozzini C, Fratta Pasini A, Garbin U, Stranieri C, Pasini A, Vallerio P, Cominacini L. Increased endoplasmic reticulum stress and Nrf2 repression in peripheral blood mononuclear cells of patients with stable coronary artery disease. Free Radic Biol Med 2014;68:178-185.
38. Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H, Negishi T, Sugawara A, Kensler TW, Yamamoto M. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol 2013;33:2996-3010.
39. Yagishita Y, Fukutomi T, Sugawara A, Kawamura H, Takahashi T, Pi J, Uruno A, Yamamoto M. Nrf2 protects pancreatic beta-cells from oxidative and nitrosative stress in diabetic model mice. Diabetes 2014;63:605-618.
40. Ruotsalainen AK, Inkala M, Partanen ME, Lappalainen JP, Kansanen E, Makinen PI, Heinonen SE, Laitinen HM, Heikkila J, Vatanen T, Horkko S, Yamamoto M, Yla-Herttuala S, Jauhiainen M, Levonen AL. The absence of macrophage Nrf2 promotes early atherogenesis. Cardiovasc Res 2013;98:107-115.
41. Ashino T, Yamamoto M, Yoshida T, Numazawa S. Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia. Arterioscler Thromb Vasc Biol 2013;33:760-768.
42. Exner M, Minar E, Wagner O, Schillinger M. The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med 2004;37:1097-1104.
43. Chen YH, Lin SJ, LinMW, Tsai HL, Kuo SS, Chen JW, Charng MJ, Wu TC, Chen LC, Ding YA, Pan WH, Jou YS, Chau LY. Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum Genet 2002;111:1-8.
44. Ono K, Goto Y, Takagi S, Baba S, Tago N, Nonogi H, Iwai N. A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Atherosclerosis 2004;173:315-319.
45. Zhang GH, Chen SM, Wang DM, Huang XS. 413A/T polymorphism in heme oxygenase-1 gene promoter is related to susceptibility of coronary artery disease in patients with dyslipidemia. Chinese Journal of Arteriosclerosis 2010;18: 63-66.
46. Qiao H, Sai X, Gai L, Huang G, Chen X, Tu X, Ding Z. Association between heme oxygenase 1 gene promoter polymorphisms and susceptibility to coronary artery disease: A HuGE review and meta-analysis. Am J Epidemiol 2014;179:1039-1048.
47. Cheng PY, Chen JJ, Yen MH. The expression of heme oxygenase-1 and inducible nitric oxide synthase in aorta during the development of hypertension in spontaneously hypertensive rats. Am J Hypertens 2004;17:1127-1134.
48. Tiwari S, Ndisang JF. Heme oxygenase system and hypertension: A comprehensive insight. Curr Pharm Des 2014;20:1354-1369.
49. Ndisang JF, Zhao W, Wang R. Selective regulation of blood pressure by heme oxygenase-1 in hypertension. Hypertension 2002;40:315-321.
50. Wang R, Wang Z, Wu L, Hanna ST, Peterson-Wakeman R. Reduced vasorelaxant effect of carbon monoxide in diabetes and the underlying mechanisms. Diabetes 2001;50:166-174.
51. Ndisang JF, Lane N, Jadhav A. Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab 2009;296:E1029-E1041.
52. Simon T, Pogu S, Tardif V, Rigaud K, Remy S, Piaggio E, Bach JM, Anegon I, Blancou P. Carbon monoxide-treated dendritic cells decrease beta1-integrin induction on CD8(+) T cells and protect from type 1 diabetes. Eur J Immunol 2013;43:209-218.
53. Nikolic I, Saksida T, Mangano K, Vujicic M, Stojanovic I, Nicoletti F, Stosic-Grujicic S. Pharmacological application of carbon monoxide ameliorates islet-directed autoimmunity in mice via anti-inflammatory and anti-apoptotic effects. Diabetologia 2014;57:980-990.
54. Tulis DA, DuranteW, Peyton KJ, Evans AJ, Schafer AI. Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat carotid arteries. Atherosclerosis 2001;155:113-122.
55. Tulis DA, DuranteW, Liu X, Evans AJ, Peyton KJ, Schafer AI. Adenovirus-mediated heme oxygenase-1 gene delivery inhibits injury-induced vascular neointima formation. Circulation 2001;104:2710-2715.
56. Wang LJ, Lee TS, Lee FY, Pai RC, Chau LY. Expression of heme oxygenase-1 in atherosclerotic lesions. Am J Pathol 1998;152:711-720.
57. Ishikawa K, Sugawara D, Goto J, Watanabe Y, Kawamura K, Shiomi M, Itabe H, Maruyama Y. Heme oxygenase-1 inhibits atherogenesis in Watanabe heritable hyperlipidemic rabbits. Circulation 2001;104:1831-1836.
58. Ishikawa K, Sugawara D, Wang X, Suzuki K, Itabe H, Maruyama Y, Lusis AJ. Heme oxygenase-1 inhibits atherosclerotic lesion formation in LDL-receptor knockout mice. Circ Res 2001;88:506-512.
59. Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY. Adenovirusmediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104:1519-1525.
60. Yet SF, Layne MD, Liu X, Chen YH, Ith B, Sibinga NE, Perrella MA. Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J 2003;17:1759-1761.
61. Clark JE, Foresti R, Sarathchandra P, Kaur H, Green CJ, Motterlini R. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am J Physiol Heart Circ Physiol 2000;278:H643-H651.
62. Raju VS, Maines MD. Renal ischemia/reperfusion up-regulates heme oxygenase-1 (HSP32) expression and increases cGMP in rat heart. J Pharmacol Exp Ther 1996; 277:1814-1822.
63. Yet SF, Tian R, Layne MD, Wang ZY, Maemura K, Solovyeva M, Ith B, Melo LG, Zhang L, Ingwall JS, Dzau VJ, Lee ME, Perrella MA. Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res 2001;89:168-173.
64. Melo LG, Agrawal R, Zhang L, Rezvani M, Mangi AA, Ehsan A, Griese DP, Dell'Acqua G, Mann MJ, Oyama J, Yet SF, Layne MD, Perrella MA, Dzau VJ. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 2002;105:602-607.
65. Liu X, Wei J, Peng DH, Layne MD, Yet SF. Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in diabetic mice. Diabetes 2005;54: 778-784.
66. Cheng C, Noordeloos AM, Jeney V, Soares MP, Moll F, Pasterkamp G, SerruysPW, Duckers HJ.Hemeoxygenase 1 determines atherosclerotic lesion progression into a vulnerable plaque. Circulation 2009;119:3017-3027.
67. Knauert M, Vangala S, Haslip M, Lee PJ. Therapeutic applications of carbon monoxide. Oxid Med Cell Longev 2013;2013:360815.
68. Wu TW, Fung KP, Wu J, Yang CC, Weisel RD. Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins. Biochem Pharmacol 1996;51: 859-862.
69. Neuzil J, Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994;269:16712-16719.
70. Jansen T, Hortmann M, Oelze M, Opitz B, Steven S, Schell R, Knorr M, Karbach S, Schuhmacher S, Wenzel P, Munze lT, Daiber A. Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1-evidence for direct and indirect antioxidant actions of bilirubin. J Mol Cell Cardiol 2010;49:186-195.
71. Wu TW, Wu J, Li RK, Mickle D, Carey D. Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage. Biochem Cell Biol 1991;69: 683-688.
72. Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, Leffler CW, Parfenova H. HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-alpha in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 2006;291:C897-C908.
73. Motterlini R, Foresti R, Intaglietta M, Winslow RM. NO-mediated activation of heme oxygenase: Endogenous cytoprotection against oxidative stress to endothelium. Am J Physiol 1996;270:H107-H114.
74. Chrobak I, Mallarino Haeger C, Maracle M, Fredenburgh L. Pulmonary Arterial Hypertension and Oxidative Stress. "Studies on Respiratory Disorders". New York: Springer; 2014. p. 259-326.
75. Maines MD. The heme oxygenase system: A regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997;37:517-554.
76. Liu D, He Z, Wu L, Fang Y. Effects of induction/inhibition of endogenous heme oxygenase-1 on lipid metabolism, endothelial function, and atherosclerosis in rabbits on a high fat diet. J Pharmacol Sci 2012;118:14-24.
77. Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 1997;94:10919-10924.
78. Wiesel P, Patel AP, DiFonzo N, Marria PB, Sim CU, Pellacani A, Maemura K, LeBlanc BW, Marino K, Doerschuk CM, Yet S-F, Lee M-E, Perrella MA. Endotoxin-induced mortality is related to increased oxidative stress and end-organ dysfunction, not refractory hypotension, in heme oxygenase-1-deficient mice. Circulation 2000;102:3015-3022.
79. Otterbein L, Chin BY, Otterbein SL, Lowe VC, Fessler HE, Choi AM. Mechanism of hemoglobin-induced protection against endotoxemia in rats: A ferritin-independent pathway. Am J Physiol 1997;272:L268-L275.
80. Otterbein L, Sylvester SL, Choi AM. Hemoglobin provides protection against lethal endotoxemia in rats: The role of heme oxygenase-1. Am J Respir Cell Mol Biol 1995; 13:595-601.
81. Sarady JK, Otterbein SL, Liu F, Otterbein LE, Choi AM. Carbonmonoxidemodulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol 2002;27:739-745.
82. Weis N, Weigert A, von Knethen A, Brune B. Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants. Mol Biol Cell 2009;20:1280-1288.
83. Vergadi E, Chang MS, Lee C, Liang OD, Liu X, Fernandez-Gonzalez A, Mitsialis SA, Kourembanas S. Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension. Circulation 2011;123:1986-1995.
84. Soares MP, Seldon MP, Gregoire IP, Vassilevskaia T, Berberat PO, Yu J, Tsui TY, Bach FH. Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol 2004;172:3553-3563.
85. Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, Usheva A, Stachulak C, Bodyak N, Smith RN, Csizmadia E, Tyagi S, Akamatsu Y, Flavell RJ, Billiar TR, Tzeng E, Bach FH, Choi AM, Soares MP. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 2003;9:183-190.
86. Bouche D, Chauveau C, Roussel JC, Mathieu P, Braudeau C, Tesson L, Soulillou JP, Iyer S, Buelow R, Anegon I. Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer. Transpl Immunol 2002;9: 235-238.
87. Du D, Chang S, Chen B, Zhou H, Chen ZK. Adenovirus-mediated heme oxygenase transfer inhibits graft arteriosclerosis in rat aortic transplants. Transplant Proc 2007; 39:3446-3448.
88. Ollinger R, Bilban M, Erat A, Froio A, McDaid J, Tyagi S, Csizmadia E, Graca-Souza AV, Liloia A, Soares MP, Otterbein LE, Usheva A, Yamashita K, Bach FH. Bilirubin: A natural inhibitor of vascular smooth muscle cell proliferation. Circulation 2005;112:1030-1039.
89. Ollinger R, Yamashita K, Bilban M, Erat A, Kogler P, Thomas M, Csizmadia E, Usheva A, Margreiter R, Bach FH. Bilirubin and biliverdin treatment of atherosclerotic diseases. Cell Cycle 2007;6:39-43.
90. Nakao A, Murase N, Ho C, Toyokawa H, Billiar TR, Kanno S. Biliverdin administration prevents the formation of intimal hyperplasia induced by vascular injury. Circulation 2005;112:587-591.
91. Fu YY, Kang KJ, Ahn JM, Kim HR, Na KY, ChaeDW, Kim S, Chin HJ. Hyperbilirubinemia reduces the streptozotocin-induced pancreatic damage through attenuating the oxidative stress in the Gunn rat. Tohoku J Exp Med 2010;222:265-273.
92. Fujii M, Inoguchi T, Sasaki S, Maeda Y, Zheng J, Kobayashi K, Takayanagi R. Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase. Kidney Int 2010;78:905-919.
93. Fukui M, Tanaka M, Shiraishi E, Harusato I, Hosoda H, Asano M, Hasegawa G, Nakamura N. Relationship between serum bilirubin and albuminuria in patients with type 2 diabetes. Kidney Int 2008;74:1197-1201.
94. Kwon KM, Kam JH, KimMY, Chung CH, Kim JK, Linton JA, Eom A, Koh SB, Kang HT. Inverse association between total bilirubin and metabolic syndrome in rural korean women. J Womens Health (Larchmt) 2011;20:963-969.
95. Wu Y, Li M, Xu M, Bi Y, Li X, Chen Y, Ning G, Wang W. Low serum total bilirubin concentrations are associated with increased prevalence of metabolic syndrome in Chinese. J Diabetes 2011;3:217-224.
96. Hayashi S, Takamiya R, Yamaguchi T, Matsumoto K, Tojo SJ, TamataniT, Kitajima M, Makino N, Ishimura Y, Suematsu M. Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res 1999;85:663-671.
97. Mazzone GL, Rigato I, Ostrow JD, Bossi F, Bortoluzzi A, Sukowati CH, Tedesco F, Tiribelli C. Bilirubin inhibits the TNFalpha-related induction of three endothelial adhesion molecules. Biochem Biophys Res Commun 2009;386:338-344.
98. Sato K, Balla J, Otterbein L, Smith RN, Brouard S, Lin Y, Csizmadia E, Sevigny J, Robson SC, Vercellotti G, Choi AM, Bach FH, Soares MP. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol 2001;166:4185-4194.
99. Silva G, Cunha A, Gregoire IP, Seldon MP, Soares MP. The antiapoptotic effect of heme oxygenase-1 in endothelial cells involves the degradation of p38 alpha MAPK isoform. J Immunol 2006;177:1894-1903.
100. Yet SF, Melo LG, Layne MD, Perrella MA.Hemeoxygenase 1 in regulation of inflammation and oxidative damage. Methods Enzymol 2002;353:163-176.
101. Liu XM, Chapman GB, Wang H, Durante W. Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells. Circulation 2002;105:79-84.
102. Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W. Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 2002;55:396-405.
103. Li T, Tian H, Zhao Y, An F, Zhang L, Zhang J, Peng J, Zhang Y, Guo Y. Heme oxygenase-1 inhibits progression and destabilization of vulnerable plaques in a rabbit model of atherosclerosis. Eur J Pharmacol 2011;672:143-152.
104. Togane Y, Morita T, Suematsu M, Ishimura Y, Yamazaki JI, Katayama S. Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury. Am J Physiol Heart Circ Physiol 2000;278:H623-H632.
105. Rodriguez AI, Gangopadhyay A, Kelley EE, Pagano PJ, Zuckerbraun BS, Bauer PM. HO-1 and CO decrease platelet-derived growth factor-induced vascular smooth muscle cell migration via inhibition of Nox1. Arterioscler Thromb Vasc Biol 2010; 30:98-104.
106. Deramaudt BM, Braunstein S, Remy P, Abraham NG. Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem 1998;68:121-127.
107. Bussolati B, Ahmed A, Pemberton H, Landis RC, DiCarlo F, Haskard DO, Mason JC. Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration. Blood 2004;103:761-766.
108. Li Volti G, Sacerdoti D, Sangras B, Vanella A, Mezentsev A, Scapagnini G, Falck JR, Abraham NG. Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells. Antioxid Redox Signal 2005;7:704-710.
109. Lin HH, Chen YH, Yet SF, Chau LY. After vascular injury, heme oxygenase-1/carbon monoxide enhances re-endothelialization via promoting mobilization of circulating endothelial progenitor cells. J Thromb Haemost 2009;7:1401-1408.
110. Wu BJ, Midwinter RG, Cassano C, Beck K, Wang Y, Changsiri D, Gamble JR, Stocker R. Heme oxygenase-1 increases endothelial progenitor cells. Arterioscler Thromb Vasc Biol 2009;29:1537-1542.
111. Lindenblatt N, Bordel R, Schareck W, Menger MD, Vollmar B. Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo. Arterioscler Thromb Vasc Biol 2004;24:601-606.
112. Peng L, Mundada L, Stomel JM, Liu JJ, Sun J, Yet SF, Fay WP. Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis. Antioxid Redox Signal 2004;6:729-735.
113. Chen YH, Tsai HL, ChiangMT, Chau LY. Carbon monoxide-induced early thrombolysis contributes to heme oxygenase-1-mediated inhibition of neointimal growth after vascular injury in hypercholesterolemic mice. J Biomed Sci 2006;13:721-730.
114. Chen B, Guo L, Fan C, Bolisetty S, Joseph R, Wright MM, Agarwal A, George JF. Carbon monoxide rescues heme oxygenase-1-deficient mice from arterial thrombosis in allogeneic aortic transplantation. Am J Pathol 2009;175:422-429.
115. Tracz MJ, Juncos JP, Grande JP, Croatt AJ, Ackerman AW, Katusic ZS, Nath KA. Induction of heme oxygenase-1 is a beneficial response in a murine model of venous thrombosis. Am J Pathol 2008;173:1882-1890.
116. True AL, Olive M, Boehm M, San H, Westrick RJ, Raghavachari N, Xu X, Lynn EG, SackMN, Munson PJ, Gladwin MT, Nabel EG. Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide. Circ Res 2007;101:893-901.
117. Sabaawy HE, Zhang F, Nguyen X, ElHosseiny A, Nasjletti A, Schwartzman M, Dennery P, Kappas A, Abraham NG. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats. Hypertension 2001;38:210-215.
118. Johnson RA, Lavesa M, DeSeyn K, Scholer MJ, Nasjletti A. Heme oxygenase substrates acutely lower blood pressure in hypertensive rats. Am J Physiol 1996;271: H1132-H1138.
119. Furchgott RF, Jothianandan D. Endothelium-dependent and -independent vasodilation involving cyclicGMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 1991;28:52-61.
120. Lin H, McGrath JJ. Vasodilating effects of carbon monoxide. Drug Chem Toxicol 1988; 11:371-385.
121. Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y. Carbon monoxide: An endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 1995;96:2431-2437.
122. Leffler CW, Nasjletti A, Yu C, Johnson RA, Fedinec AL, Walker N. Carbon monoxide and cerebral microvascular tone in newborn pigs. Am J Physiol 1999;276: H1641-H1646.
123. Kozma F, Johnson RA, Nasjletti A. Role of carbon monoxide in heme-induced vasodilation. Eur J Pharmacol 1997;323:R1-R2.
124. Graser T, Vedernikov YP, Li DS. Study on the mechanism of carbon monoxide induced endothelium-independent relaxation in porcine coronary artery and vein. Biomed Biochim Acta 1990;49:293-296.
125. 2+ sensitivity of alpha-subunits. Am J Physiol Heart Circ Physiol 2004; 286:H610-H618.
126. Morita T, Kourembanas S. Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 1995;96:2676-2682.
127. Johnson FK, Johnson RA. Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles. Am J Physiol Regul Integr Comp Physiol 2003;285:R536-R541.
128. Ishikawa M, Kajimura M, Adachi T, Maruyama K, Makino N, Goda N, Yamaguchi T, Sekizuka E, Suematsu M. Carbon monoxide from hemeoxygenase-2 is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation. Circ Res 2005;97:e104-e114.
129. Favatier F, Polla BS. Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates. Biochem J 2001;353:475-482.
130. Jonas JC, Guiot Y, Rahier J, Henquin JC. Haeme-oxygenase 1 expression in rat pancreatic beta cells is stimulated by supraphysiological glucose concentrations and by cyclic AMP. Diabetologia 2003;46:1234-1244.
131. Ishizaka N, de Leon H, Laursen JB, Fukui T, Wilcox JN, De Keulenaer G, Griendling KK, Alexander RW. Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta. Circulation 1997;96:1923-1929.
132. Bao W, Song F, Li X, Rong S, Yang W, Zhang M, Yao P, Hao L, Yang N, Hu FB, Liu L. Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus. PLoS ONE 2010;5:e12371.
133. Avogaro A, Pagnin E, Calo L. Monocyte NADPH oxidase subunit p22(phox) and inducible hemeoxygenase-1 gene expressions are increased in type II diabetic patients: relationship with oxidative stress. J Clin Endocrinol Metab 2003;88: 1753-1759.
134. Ndisang JF, Jadhav A. Up-regulating the hemeoxygenase system enhances insulin sensitivity and improves glucose metabolism in insulin-resistant diabetes in Goto- Kakizaki rats. Endocrinology 2009;150:2627-2636.
135. Li M, Kim DH, Tsenovoy PL, Peterson SJ, Rezzani R, Rodella LF, Aronow WS, Ikehara S, Abraham NG. Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes 2008;57: 1526-1535.
136. Nicolai A, Li M, Kim DH, Peterson SJ, Vanella L, PositanoV, Gastaldelli A, Rezzani R, Rodella LF, Drummond G, Kusmic C, L'Abbate A, Kappas A, Abraham NG.. Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats Hypertension 2009;53:508-515.
137. Ndisang JF, Jadhav A. Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes. Am J Physiol Endocrinol Metab 2009;296:E829-E841.
138. Burgess A, Li M, Vanella L, Kim DH, Rezzani R, Rodella L, Sodhi K, Canestraro M, Martasek P, Peterson SJ, Kappas A, Abraham NG. Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice. Hypertension 2010;56:1124-1130.
139. Basuroy S, Bhattacharya S, Leffler CW, Parfenova H. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-alpha in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 2009;296:C422-C432.
140. Jais A, Einwallner E, Sharif O, Gossens K, Lu TT, Soyal SM, Medgyesi D, Neureiter D, Paier-Pourani J, Dalgaard K, Duvigneau JC, Lindroos-Christensen J, Zapf TC, Amann S, Saluzzo S, Jantscher F, Stiedl P, Todoric J, Martins R, Oberkofler H, Muller S, Hauser-Kronberger C, Kenner L, Casanova E, Sutterluty-Fall H, Bilban M, Miller K, Kozlov AV, Krempler F, Knapp S, Lumeng CN, Patsch W, Wagner O, Pospisilik JA, Esterbauer H. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell 2014;158:25-40.
141. Teupser D, Weber O, Rao TN, Sass K, Thiery J, Fehling HJ.Noreduction of atherosclerosis in C-reactive protein (CRP)-deficient mice. J Biol Chem 2011;286: 6272-6279.
142. Chida D, Osaka T, Hashimoto O, Iwakura Y. Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice. Diabetes 2006;55:971-977.
143. Newton-Cheh C, Larson MG, Vasan RS, Levy D, Bloch KD, Surti A, Guiducci C, Kathiresan S, Benjamin EJ, Struck J, Morgenthaler NG, Bergmann A, Blankenberg S, Kee F, Nilsson P, Yin X, Peltonen L, Vartiainen E, Salomaa V, Hirschhorn JN, Melander O, Wang TJ. Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nat Genet 2009;41:348-353.
144. Cheng S, Enserro D, Xanthakis V, Sullivan LM, Murabito JM, Benjamin EJ, Polak JF, O'Donnell CJ, Wolf PA, O'Connor GT, Keaney JF, Vasan RS. Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes. Eur Heart J 2014;35: 2980-2987.
145. Cheng S, Lyass A, Massaro JM, O'Connor GT, Keaney JF Jr, Vasan RS. Exhaled carbon monoxide and risk of metabolic syndrome and cardiovascular disease in the community. Circulation 2010;122:1470-1477.
146. Stocker R, Perrella MA. Heme oxygenase-1: A novel drug target for atherosclerotic diseases? Circulation 2006;114:2178-2189.
147. Grosser N, Abate A, Oberle S, Vreman HJ, Dennery PA, Becker JC, Pohle T, Seidman DS, Schroder H. Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem Biophys Res Commun 2003;308:956-960.
148. Ono K, Mannami T, Iwai N. Association of a promoter variant of the haeme oxygenase-1 gene with hypertension in women. J Hypertens 2003;21:1497-1503.
149. Yun L, Xiaoli L, Qi Z, Laiyuan W, Xiangfeng L, Chong S, Jianfeng H, Shufeng C, Hongfan L, Gu D. Association of an intronic variant of the heme oxygenase-1 gene with hypertension in northern Chinese Han population. Clin Exp Hypertens 2009;31:534-543.
150. Lin R, Fu W, Zhou W, Wang Y, Wang X, Huang W, Jin L. Association of heme oxygenase-1 gene polymorphisms with essential hypertension and blood pressure in the Chinese Han population. Genet Test Mol Biomarkers 2011;15:23-28.
151. Haghdoost F, Javanmard SH, Keyhanian K, Samety AA, Loghmani P, Rafiei L, Sarrafzadegan N. Association of heme oxygenase-1 gene promoter polymorphism and blood pressure in an Iranian population. Intern Med J 2014;44:931-932.
152. Wu MM, Chiou HY, Chen CL, Hsu LI, Lien LM, Wang CH, Hsieh YC, Wang YH, Hsueh YM, Lee TC, Cheng WF, Chen CJ. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: An observation based on arsenic-exposed individuals. Atherosclerosis 2011;219:704-708.
153. Javanmard SH, Keyhanian K, Loghmani P, Samety AA, Haghdoost F, Rafiei L, Talaei M, Asgari S, Jazi MH, Sarrafzadegan N. Association between heme oxygenase-1 gene promoter polymorphisms and metabolic syndrome in Iranians. Mol Biol Rep 2012;39:3355-3360.
154. Arredondo M, Fuentes M, Jorquera D, Candia V, Carrasco E, Leiva E, Mujica V, Hertrampf E, Perez F. Cross-talk between body iron stores and diabetes: iron stores are associated with activity and microsatellite polymorphism of the heme oxygenase and type 2 diabetes. Biol Trace Elem Res 2011;143:625-636.
155. Song F, Li X, Zhang M, Yao P, Yang N, Sun X, Hu FB, Liu L. Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes in a Chinese population. Am J Epidemiol 2009;170:747-756.
156. Arredondo M, Jorquera D, Carrasco E, Albala C, Hertrampf E. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with iron status in persons with type 2 diabetes mellitus. Am J Clin Nutr 2007;86:1347-1353.
157. Choi SW, Yeung VT, Benzie IF.Hemeoxygenase microsatellite polymorphism, oxidative stress, glycemic control, and complication development in type 2 diabetes patients. Free Radic Biol Med 2012;53:60-63.
158. Chen YH, Chau LY, Chen JW, Lin SJ. Serum bilirubin and ferritin levels link heme oxygenase-1 gene promoter polymorphism and susceptibility to coronary artery disease in diabetic patients. Diabetes Care 2008;31:1615-1620.
159. Kaneda H, Ohno M, Taguchi J, Togo M, Hashimoto H, Ogasawara K, Aizawa T, Ishizaka N, Nagai R. Heme oxygenase-1 gene promoter polymorphism is associated with coronary artery disease in Japanese patients with coronary risk factors. Arterioscler Thromb Vasc Biol 2002;22:1680-1685.
160. Lublinghoff N, Winkler K, Winkelmann BR, Seelhorst U, Wellnitz B, Boehm BO, Marz W, Hoffmann MM. Genetic variants of the promoter of the heme oxygenase-1 gene and their influence on cardiovascular disease (the Ludwigshafen Risk and Cardiovascular Health study). BMC Med Genet 2009;10:36.
161. Brydun A, Watari Y, Yamamoto Y, Okuhara K, Teragawa H, Kono F, Chayama K, Oshima T, Ozono R. Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis. Hypertens Res 2007;30:341-348.
162. Endler G, Exner M, Schillinger M, Marculescu R, Sunder-Plassmann R, Raith M, Jordanova N, Wojta J, Mannhalter C, Wagner OF, Huber K. A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with increased bilirubin and HDL levels but not with coronary artery disease. Thromb Haemost 2004;91:155-161.
163. Liang KW, Sheu WH, Lee WL, Lee IT, Lin SY, Ting CT, Lee WJ. Shorter GTrepeats in the heme oxygenase-1 gene promoter are associated with a lower severity score in coronary artery disease. J Chin Med Assoc 2013;76:312-318.
164. Chen M, Zhou L, Ding H, Huang S, He M, Zhang X, Cheng L, Wang D, Hu FB, Wu T. Short (GT) (n) repeats in heme oxygenase-1 gene promoter are associated with lower risk of coronary heart disease in subjects with high levels of oxidative stress. Cell Stress Chaperones 2012;17:329-338.
165. Bai CH, Chen JR, Chiu HC, Chou CC, Chau LY, Pan WH. Shorter GT repeat polymorphism in the heme oxygenase-1 gene promoter has protective effect on ischemic stroke in dyslipidemia patients. J Biomed Sci 2010;17:12.
166. Funk M, Endler G, Schillinger M, Mustafa S, Hsieh K, Exner M, Lalouschek W, Mannhalter C, Wagner O. The effect of a promoter polymorphism in the heme oxygenase-1 gene on the risk of ischaemic cerebrovascular events: The influence of other vascular risk factors. Thromb Res 2004;113:217-223.
167. Chen YH, Hung SC, Tarng DC. Length polymorphism in heme oxygenase-1 and cardiovascular events and mortality in hemodialysis patients. Clin J Am Soc Nephrol 2013;8:1756-1763.
168. Dick P, Schillinger M, Minar E, MlekuschW, Amighi J, Sabeti S, Schlager O, Raith M, Endler G, Mannhalter C, Wagner O, Exner M. Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease. Eur J Clin Invest 2005;35:731-737.
169. Kral A, Kovarnik T, Kralik L, Skalicka H, Horak J, Mintz GS, Uhrova J, Sonka M, Wahle A, Downe R, Aschermann M, Martasek P, Linhart A. Genetic variants in haem oxygenase-1 and endothelial nitric oxide synthase influence the extent and evolution of coronary artery atherosclerosis. Folia Biol (Praha) 2011;57:182-190.
170. Wu MM, Chiou HY, Lee TC, Chen CL, Hsu LI, Wang YH, Huang WL, Hsieh YC, Yang TY, Lee CY, Yip PK, Wang CH, Hsueh YM, Chen CJ. GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure. J Biomed Sci 2010;17:70.
171. Wu MM, Chiou HY, Chen CL, Wang YH, Hsieh YC, Lien LM, Lee TC, Chen CJ. GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposedpopulation in northeastern Taiwan. Toxicol Appl Pharmacol 2010;248:226-233.
172. Chen YH, Chau LY, Lin MW, Chen LC, Yo MH, Chen JW, Lin SJ.Hemeoxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting. Eur Heart J 2004;25:39-47.
173. Gulesserian T, Wenzel C, Endler G, Sunder-Plassmann R, Marsik C, Mannhalter C, Iordanova N, Gyongyosi M, Wojta J, Mustafa S, Wagner O, Huber K. Clinical restenosis after coronary stent implantation is associated with the heme oxygenase-1 gene promoter polymorphism and the heme oxygenase-1 +99G/C variant. Clin Chem 2005;51:1661-1665.
174. Tiroch K, Koch W, von Beckerath N, Kastrati A, Schomig A. Heme oxygenase-1 gene promoter polymorphism and restenosis following coronary stenting. Eur Heart J 2007;28:968-973.
175. Schillinger M, Exner M, Minar E, MlekuschW, Mullner M, Mannhalter C, Bach FH, Wagner O.Hemeoxygenase-1 genotype and restenosis after balloon angioplasty: A novel vascular protective factor. J Am Coll Cardiol 2004;43:950-957.
176. Schillinger M, Exner M, Mlekusch W, Ahmadi R, Rumpold H, Mannhalter C, Wagner O, Minar E. Heme oxygenase-1 genotype is a vascular anti-inflammatory factor following balloon angioplasty. J Endovasc Ther 2002;9:385-394.
177. Exner M, Schillinger M, Minar E, MlekuschW, Schlerka G, Haumer M, Mannhalter C, Wagner O.Hemeoxygenase-1 gene promoter microsatellite polymorphismis associated with restenosis after percutaneous transluminal angioplasty. J Endovasc Ther 2001;8:433-440.
178. Li P, Elrayess MA, Gomma AH, Palmen J, Hawe E, Fox KM, Humphries SE. The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting. Chin Med J (Engl) 2005;118:1525-1532.
179. Guzek M, Jakubowski Z, Bandosz P, Wyrzykowski B, Smoczynski M, Jabloiska A, Zdrojewski T. Inverse association of serum bilirubin with metabolic syndrome and insulin resistance in Polish population. Przegl Epidemiol 2012;66:495-501.
180. Choi SH, Yun KE, Choi HJ. Relationships between serum total bilirubin levels and metabolic syndrome in Korean adults. Nutr Metab Cardiovasc Dis 2013;23:31-37.
181. Jo J, Yun JE, Lee H, Kimm H, Jee SH. Total, direct, and indirect serum bilirubin concentrations and metabolic syndrome among the Korean population. Endocrine 2011;39:182-189.
182. Hwang HJ, Kim SH. Inverse relationship between fasting direct bilirubin and metabolic syndrome in Korean adults. Clin Chim Acta 2010;411:1496-1501.
183. Lin LY, Kuo HK, Hwang JJ, Lai LP, Chiang FT, Tseng CD, Lin JL. Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents. Atherosclerosis 2009;203:563-568.
184. Choi SW, Lee YH, Kweon SS, Song HR, Ahn HR, Rhee JA, Choi JS, Shin MH. Association between total bilirubin and hemoglobin A1c in Korean type 2 diabetic patients. J Korean Med Sci 2012;27:1196-1201.
185. Sheu WH, Chen YT, Lee WJ, Wang CW, Lin LY. Arelationship between serum ferritin and the insulin resistance syndrome is present in non-diabetic women but not in non-diabetic men. Clin Endocrinol (Oxf) 2003;58:380-385.
186. Jung CH, Lee MJ, Kang YM, Hwang JY, Jang JE, Leem J, Park JY, Kim HK, Lee WJ. Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study. Metabolism 2014; 63:87-93.
187. Kim KM, Kim BT, Park SB, Cho DY, Je SH, Kim KN. Serum total bilirubin concentration is inversely correlated with Framingham risk score in Koreans. Arch Med Res 2012;43:288-293.
188. Djousse L, Levy D, Cupples LA, Evans JC, D'Agostino RB, Ellison RC. Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study. Am J Cardiol 2001;87:1196-1200.
189. Horsfall LJ, Nazareth I, Petersen I. Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation 2012;126:2556-2564.
190. Kunutsor SK, Bakker SJ, Gansevoort RT, Chowdhury R, Dullaart RP. Circulating total bilirubin and risk of incident cardiovascular disease in the general population. Arterioscler Thromb Vasc Biol 2015;35:716-724.
191. Hedblad B, Engstrom G, Janzon E, Berglund G, Janzon L. COHb% as a marker of cardiovascular risk in never smokers: results from a population-based cohort study. Scand J Public Health 2006;34:609-615.
192. Troughton JA, Woodside JV, Young IS, Arveiler D, Amouyel P, Ferrieres J, Ducimetiere P, Patterson CC, Kee F, Yarnell JW, Evans A, Group PS. Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Eur J Cardiovasc Prev Rehabil 2007;14:79-84.
193. Jorgensen ME, Torp-Pedersen C, Finer N, Caterson I, James WP, Legler UF, Andersson C. Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial. Nutr Metab Cardiovasc Dis 2014;24:656-662.