Red blood cell, hemoglobin and heme in the progression of atherosclerosis

Frontiers in Physiology

Volumn 5, Issue OCT, 2014, Pages

  Jeney, Viktória ^a,b   Balla, György ^b,c   Balla, József ^a  

^a UNIVERSITY OF DEBRECEN   (Hungary)

^b INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^c UNIVERSITY OF DEBRECEN   (Hungary)

Author keywords

Atherosclerosis; Ferritin; Haptoglobin; Heme oxygenase; Hemoglobin oxidation; Hemopexin; Intraplaque hemorrhage; Red blood cell lysis

Indexed keywords

ALPHA 1 MICROGLOBULIN; CHOLESTEROL; FERRITIN; HAPTOGLOBIN; HEME; HEME OXYGENASE 1; HEMOGLOBIN; HEMOPEXIN; REACTIVE OXYGEN METABOLITE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 6;

ADAPTATION; ANGIOGENESIS; ATHEROSCLEROSIS; AUTOOXIDATION; BLEEDING; CELL DAMAGE; DEFENSE MECHANISM; ENDOTHELIUM CELL; ERYTHROCYTE MEMBRANE; HEMOLYSIS; HUMAN; HYPOXIA; INFLAMMATION; INTERMITTENT HYPOXIA; INTRAPLAQUE HEMORRHAGE; LIPID PEROXIDATION; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; PROTEIN SECRETION; REVIEW; SUSTAINED HYPOXIA;

EID: 84908376176     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2014.00379     Document Type: Review

References (149)

1. Agarwal, A., Balla, J., Balla, G., Croatt, A. J., Vercellotti, G. M., and Nath, K. A. (1996). Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL. Am. J. Physiol. 271, F814-F823.
2. Akerstrom, B., and Gram, M. (2014). A1M, an extravascular tissue cleaning and housekeeping protein. Free Radic. Biol. Med. 74C, 274-282. doi: 10.1016/j.freeradbiomed.2014.06.025
3. Alam, J., and Smith, A. (1989). Receptor-mediated transport of heme by hemopexin regulates gene expression in mammalian cells. J. Biol. Chem. 264, 17637-17640.
4. Alayash, A. I. (2011). Haptoglobin: Old protein with new functions. Clin. Chim. Acta 412, 493-498. doi: 10.1016/j.cca.2010.12.011
5. Alayash, A. I., Patel, R. P., and Cashon, R. E. (2001). Redox reactions of hemoglobin and myoglobin: biological and toxicological implications. Antioxid. Redox Signal. 3, 313-327. doi: 10.1089/152308601300185250
6. Allhorn, M., Berggard, T., Nordberg, J., Olsson, M. L., and Akerstrom, B. (2002). Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties. Blood 99, 1894-1901. doi: 10.1182/blood.V99.6.1894
7. Andersen, C. B., Torvund-Jensen, M., Nielsen, M. J., de Oliveira, C. L., Hersleth, H. P., Andersen, N. H., et al. (2012). Structure of the haptoglobin-haemoglobin complex. Nature 489, 456-459. doi: 10.1038/nature11369
8. Arruda, M. A., Graca-Souza, A. V., and Barja-Fidalgo, C. (2005). Heme and innate immunity: new insights for an old molecule. Mem. Inst. Oswaldo Cruz 100, 799-803. doi: 10.1590/S0074-02762005000700022
9. Asleh, R., Marsh, S., Shilkrut, M., Binah, O., Guetta, J., Lejbkowicz, F., et al. (2003). Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circ. Res. 92, 1193-1200. doi: 10.1161/01.RES.0000076889.23082.F1
10. Balla, G., Jacob, H. S., Balla, J., Rosenberg, M., Nath, K., Apple, F., et al. (1992b). Ferritin: a cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267, 18148-18153.
11. Balla, G., Jacob, H. S., Eaton, J. W., Belcher, J. D., and Vercellotti, G. M. (1991a). Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury. Arterioscler. Thromb. 11, 1700-1711.
12. Balla, G., Vercellotti, G., Eaton, J. W., and Jacob, H. S. (1990). Heme uptake by endothelium synergizes polymorphonuclear granulocyte-mediated damage. Trans. Assoc. Am. Physicians 103, 174-179.
13. Balla, G., Vercellotti, G. M., Muller-Eberhard, U., Eaton, J., and Jacob, H. S. (1991b). Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species. Lab. Invest. 64, 648-655.
14. Balla, J., Jacob, H. S., Balla, G., Nath, K., Eaton, J. W., and Vercellotti, G. M. (1993). Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc. Natl. Acad. Sci. U.S.A. 90, 9285-9289. doi: 10.1073/pnas.90.20.9285
15. Balla, J., Jacob, H. S., Balla, G., Nath, K., and Vercellotti, G. M. (1992a). Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage. Trans. Assoc. Am. Physicians 105, 1-6.
16. Balla, J., Vercellotti, G. M., Jeney, V., Yachie, A., Varga, Z., Jacob, H. S., et al. (2007). Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment. Antioxid. Redox Signal. 9, 2119-2137. doi: 10.1089/ars.2007.1787
17. Bamm, V. V., Tsemakhovich, V. A., Shaklai, M., and Shaklai, N. (2004). Haptoglobin phenotypes differ in their ability to inhibit heme transfer from hemoglobin to LDL. Biochemistry 43, 3899-3906. doi: 10.1021/bi0362626
18. Banerjee, S., Jia, Y., Siburt, C. J., Abraham, B., Wood, F., Bonaventura, C., et al. (2012). Haptoglobin alters oxygenation and oxidation of hemoglobin and decreases propagation of peroxide-induced oxidative reactions. Free Radic. Biol. Med. 53, 1317-1326. doi: 10.1016/j.freeradbiomed.2012.07.023
19. Belcher, J. D., Chen, C., Nguyen, J., Milbauer, L., Abdulla, F., Alayash, A. I., et al. (2014). Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood 123, 377-390. doi: 10.1182/blood-2013-04-495887
20. Bhandaru, R., Srinivasan, S. R., Radhakrisnamurthy, B., and Berenson, G. S. (1982). Effects of diabetes and high fat-high cholesterol diet on plasma lipid levels and on erythrocyte membrane composition. Atherosclerosis 42, 263-272. doi: 10.1016/0021-9150(82)90156-3
21. Bjornheden, T., Levin, M., Evaldsson, M., and Wiklund, O. (1999). Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler. Thromb. Vasc. Biol. 19, 870-876. doi: 10.1161/01.ATV.19.4.870
22. Bochkov, V. N., Philippova, M., Oskolkova, O., Kadl, A., Furnkranz, A., Karabeg, E., et al. (2006). Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions. Circ. Res. 99, 900-908. doi: 10.1161/01.RES.0000245485.04489.ee
23. Bordon, Y. (2010). A new vein of TLR biology. Nat. Rev. Immunol. 10:748. doi: 10.1038/nri2875
24. Bot, I., Jukema, J. W., Lankhuizen, I. M., van Berkel, T. J., and Biessen, E. A. (2011). Atorvastatin inhibits plaque development and adventitial neovascularization in ApoE deficient mice independent of plasma cholesterol levels. Atherosclerosis 214, 295-300. doi: 10.1016/j.atherosclerosis.2010.11.008
25. Boyle, J. J., Harrington, H. A., Piper, E., Elderfield, K., Stark, J., Landis, R. C., et al. (2009). Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype. Am. J. Pathol. 174, 1097-1108. doi: 10.2353/ajpath.2009.080431
26. Boyle, J. J., Johns, M., Kampfer, T., Nguyen, A. T., Game, L., Schaer, D. J., et al. (2012). Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection. Circ. Res. 110, 20-33. doi: 10.1161/CIRCRESAHA.111.247577
27. Buehler, P. W., Abraham, B., Vallelian, F., Linnemayr, C., Pereira, C. P., Cipollo, J. F., et al. (2009). Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification. Blood 113, 2578-2586. doi: 10.1182/blood-2008-08-174466
28. Bunn, H. F., and Jandl, J. H. (1968). Exchange of heme among hemoglobins and between hemoglobin and albumin. J. Biol. Chem. 243, 465-475.
29. Caspar-Bauguil, S., Garcia, J., Galinier, A., Periquet, B., Ferrieres, J., Allenbach, S., et al. (2010). Positive impact of long-term lifestyle change on erythrocyte fatty acid profile after acute coronary syndromes. Arch. Cardiovasc. Dis. 103, 106-114. doi: 10.1016/j.acvd.2009.12.005
30. Celletti, F. L., Waugh, J. M., Amabile, P. G., Brendolan, A., Hilfiker, P. R., and Dake, M. D. (2001). Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat. Med. 7, 425-429. doi: 10.1038/86490
31. Cheng, C., Noordeloos, A. M., Jeney, V., Soares, M. P., Moll, F., Pasterkamp, G., et al. (2009). Heme oxygenase 1 determines atherosclerotic lesion progression into a vulnerable plaque. Circulation 119, 3017-3027. doi: 10.1161/CIRCULATIONAHA.108.808618
32. Costacou, T., and Levy, A. P. (2012). Haptoglobin genotype and its role in diabetic cardiovascular disease. J. Cardiovasc. Transl. Res. 5, 423-435. doi: 10.1007/s12265-012-9361-z
33. Crawford, D. W., and Blankenhorn, D. H. (1991). Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis 89, 97-108. doi: 10.1016/0021-9150(91)90049-9
34. Deterding, L. J., Ramirez, D. C., Dubin, J. R., Mason, R. P., and Tomer, K. B. (2004). Identification of free radicals on hemoglobin from its self-peroxidation using mass spectrometry and immuno-spin trapping: observation of a histidinyl radical. J. Biol. Chem. 279, 11600-11607. doi: 10.1074/jbc.M310704200
35. Drinane, M., Mollmark, J., Zagorchev, L., Moodie, K., Sun, B., Hall, A., et al. (2009). The antiangiogenic activity of rPAI-1(23) inhibits vasa vasorum and growth of atherosclerotic plaque. Circ. Res. 104, 337-345. doi: 10.1161/CIRCRESAHA.108.184622
36. Dunmore, B. J., McCarthy, M. J., Naylor, A. R., and Brindle, N. P. (2007). Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques. J. Vasc. Surg. 45, 155-159. doi: 10.1016/j.jvs.2006.08.072
37. Durante, W. (2010). Targeting heme oxygenase-1 in vascular disease. Curr. Drug Targets 11, 1504-1516. doi: 10.2174/1389450111009011504
38. Figueiredo, R. T., Fernandez, P. L., Mourao-Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., et al. (2007). Characterization of heme as activator of Toll-like receptor 4. J. Biol. Chem. 282, 20221-20229. doi: 10.1074/jbc.M610737200
39. Finn, A. V., Nakano, M., Polavarapu, R., Karmali, V., Saeed, O., Zhao, X., et al. (2012). Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J. Am. Coll. Cardiol. 59, 166-177. doi: 10.1016/j.jacc.2011.10.852
40. Forsythe, J. A., Jiang, B. H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., et al. (1996). Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol. Cell. Biol. 16, 4604-4613.
41. Galis, Z. S., and Lessner, S. M. (2009). Will the real plaque vasculature please stand up? Why we need to distinguish the vasa plaquorum from the vasa vasorum. Trends Cardiovasc. Med. 19, 87-94. doi: 10.1016/j.tcm.2009.06.001
42. Gao, L., Chen, Q., Zhou, X., and Fan, L. (2012). The role of hypoxia-inducible factor 1 in atherosclerosis. J. Clin. Pathol. 65, 872-876. doi: 10.1136/jclinpath-2012-200828
43. Geiringer, E. (1951). Intimal vascularization and atherosclerosis. J. Pathol. Bacteriol. 63, 201-211. doi: 10.1002/path.1700630204
44. Goldenstein, H., Levy, N. S., and Levy, A. P. (2012). Haptoglobin genotype and its role in determining heme-iron mediated vascular disease. Pharmacol. Res. 66, 1-6. doi: 10.1016/j.phrs.2012.02.011
45. Gozzelino, R., Jeney, V., and Soares, M. P. (2010). Mechanisms of cell protection by heme oxygenase-1. Annu. Rev. Pharmacol. Toxicol. 50, 323-354. doi: 10.1146/annurev.pharmtox.010909.105600
46. Gram, M., Sveinsdottir, S., Ruscher, K., Hansson, S. R., Cinthio, M., Akerstrom, B., et al. (2013). Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation. J. Neuroinflammation 10:100. doi: 10.1186/1742-2094-10-100
47. Grote, K., Schuett, H., Salguero, G., Grothusen, C., Jagielska, J., Drexler, H., et al. (2010). Toll-like receptor 2/6 stimulation promotes angiogenesis via GM-CSF as a potential strategy for immune defense and tissue regeneration. Blood 115, 2543-2552. doi: 10.1182/blood-2009-05-224402
48. Gutteridge, J. M., and Smith, A. (1988). Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochem. J. 256, 861-865.
49. Harel, S., and Kanner, J. (1988). The generation of ferryl or hydroxyl radicals during interaction of haemproteins with hydrogen peroxide. Free Radic. Res. Commun. 5, 21-33. doi: 10.3109/10715768809068555
50. Heeschen, C., Jang, J. J., Weis, M., Pathak, A., Kaji, S., Hu, R. S., et al. (2001). Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat. Med. 7, 833-839. doi: 10.1038/89961
51. Heistad, D. D., Armstrong, M. L., and Marcus, M. L. (1981). Hyperemia of the aortic wall in atherosclerotic monkeys. Circ. Res. 48, 669-675. doi: 10.1161/01.RES.48.5.669
52. Herz, J., and Strickland, D. K. (2001). LRP: a multifunctional scavenger and signaling receptor. J. Clin. Invest. 108, 779-784. doi: 10.1172/JCI200113992
53. Higashida, T., Kanno, H., Nakano, M., Funakoshi, K., and Yamamoto, I. (2008). Expression of hypoxia-inducible angiogenic proteins (hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and E26 transformation-specific-1) and plaque hemorrhage in human carotid atherosclerosis. J. Neurosurg. 109, 83-91. doi: 10.3171/JNS/2008/109/7/0083
54. Hill-Kapturczak, N., Voakes, C., Garcia, J., Visner, G., Nick, H. S., and Agarwal, A. (2003). A cis-acting region regulates oxidized lipid-mediated induction of the human heme oxygenase-1 gene in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 23, 1416-1422. doi: 10.1161/01.ATV.0000081656.76378.A7
55. Hrkal, Z., Vodrazka, Z., and Kalousek, I. (1974). Transfer of heme from ferrihemoglobin and ferrihemoglobin isolated chains to hemopexin. Eur. J. Biochem. 43, 73-78. doi: 10.1111/j.1432-1033.1974.tb03386.x
56. Hutter, R., Speidl, W. S., Valdiviezo, C., Sauter, B., Corti, R., Fuster, V., et al. (2013). Macrophages transmit potent proangiogenic effects of oxLDL in vitro and in vivo involving HIF-1alpha activation: a novel aspect of angiogenesis in atherosclerosis. J. Cardiovasc. Transl. Res. 6, 558-569. doi: 10.1007/s12265-013-9469-9
57. Hvidberg, V., Maniecki, M. B., Jacobsen, C., Hojrup, P., Moller, H. J., and Moestrup, S. K. (2005). Identification of the receptor scavenging hemopexin-heme complexes. Blood 106, 2572-2579. doi: 10.1182/blood-2005-03-1185
58. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., et al. (2001). HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292, 464-468. doi: 10.1126/science.1059817
59. Ivanov, A. S., Torkhovskaya, T. I., Khalilov, E. M., and Archakov, A. I. (1991). Diet-induced hypercholesterolaemia in the rabbit. Biomed. Sci. 2, 285-288.
60. Jeney, V., Balla, J., Yachie, A., Varga, Z., Vercellotti, G. M., Eaton, J. W., et al. (2002). Pro-oxidant and cytotoxic effects of circulating heme. Blood 100, 879-887. doi: 10.1182/blood.V100.3.879
61. Jeney, V., Eaton, J. W., Balla, G., and Balla, J. (2013). Natural history of the bruise: formation, elimination, and biological effects of oxidized hemoglobin. Oxid. Med. Cell. Longev. 2013:703571. doi: 10.1155/2013/703571
62. Jeziorska, M., and Woolley, D. E. (1999). Neovascularization in early atherosclerotic lesions of human carotid arteries: its potential contribution to plaque development. Hum. Pathol. 30, 919-925. doi: 10.1016/S0046-8177(99)90245-9
63. Jia, Y., Buehler, P. W., Boykins, R. A., Venable, R. M., and Alayash, A. I. (2007). Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway. J. Biol. Chem. 282, 4894-4907. doi: 10.1074/jbc.M609955200
64. Juan, S. H., Lee, T. S., Tseng, K. W., Liou, J. Y., Shyue, S. K., Wu, K. K., et al. (2001). Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 104, 1519-1525. doi: 10.1161/hc3801.095663
65. Juckett, M. B., Balla, J., Balla, G., Jessurun, J., Jacob, H. S., and Vercellotti, G. M. (1995). Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro. Am. J. Pathol. 147, 782-789.
66. Julius, U., and Pietzsch, J. (2005). Glucose-induced enhancement of hemin-catalyzed LDL oxidation in vitro and in vivo. Antioxid. Redox Signal. 7, 1507-1512. doi: 10.1089/ars.2005.7.1507
67. Jun, J., Reinke, C., Bedja, D., Berkowitz, D., Bevans-Fonti, S., Li, J., et al. (2010). Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 209, 381-386. doi: 10.1016/j.atherosclerosis.2009.10.017
68. Jurrus, E. R., and Weiss, H. S. (1977). In vitro tissue oxygen tensions in the rabbit aortic arch. Atherosclerosis 28, 223-232. doi: 10.1016/0021-9150(77)90172-1
69. Kawashima, A., Oda, Y., Yachie, A., Koizumi, S., and Nakanishi, I. (2002). Heme oxygenase-1 deficiency: the first autopsy case. Hum. Pathol. 33, 125-130. doi: 10.1053/hupa.2002.30217
70. Kim, Y. W., and Byzova, T. V. (2014). Oxidative stress in angiogenesis and vascular disease. Blood 123, 625-631. doi: 10.1182/blood-2013-09-512749
71. Knighton, D. R., Hunt, T. K., Scheuenstuhl, H., Halliday, B. J., Werb, Z., and Banda, M. J. (1983). Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 221, 1283-1285. doi: 10.1126/science.6612342
72. Kockx, M. M., Cromheeke, K. M., Knaapen, M. W., Bosmans, J. M., De Meyer, G. R., Herman, A. G., et al. (2003). Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 23, 440-446. doi: 10.1161/01.ATV.0000057807.28754.7F
73. Kolodgie, F. D., Burke, A. P., Nakazawa, G., Cheng, Q., Xu, X., and Virmani, R. (2007). Free cholesterol in atherosclerotic plaques: where does it come from? Curr. Opin. Lipidol. 18, 500-507. doi: 10.1097/MOL.0b013e3282efa35b
74. Kolodgie, F. D., Gold, H. K., Burke, A. P., Fowler, D. R., Kruth, H. S., Weber, D. K., et al. (2003). Intraplaque hemorrhage and progression of coronary atheroma. N. Engl. J. Med. 349, 2316-2325. doi: 10.1056/NEJMoa035655
75. Koter, M., Broncel, M., Chojnowska-Jezierska, J., Klikczynska, K., and Franiak, I. (2002). The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia. Eur. J. Clin. Pharmacol. 58, 501-506. doi: 10.1007/s00228-002-0507-9
76. Kristiansen, M., Graversen, J. H., Jacobsen, C., Sonne, O., Hoffman, H. J., Law, S. K., et al. (2001). Identification of the haemoglobin scavenger receptor. Nature 409, 198-201. doi: 10.1038/35051594
77. Larsen, R., Gozzelino, R., Jeney, V., Tokaji, L., Bozza, F. A., Japiassu, A. M., et al. (2010). A central role for free heme in the pathogenesis of severe sepsis. Sci. Transl. Med. 2:51ra71. doi: 10.1126/scitranslmed.3001118
78. Leibovich, S. J., Chen, J. F., Pinhal-Enfield, G., Belem, P. C., Elson, G., Rosania, A., et al. (2002). Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin. Am. J. Pathol. 160, 2231-2244. doi: 10.1016/S0002-9440(10)61170-4
79. Leitinger, N., and Schulman, I. G. (2013). Phenotypic polarization of macrophages in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 33, 1120-1126. doi: 10.1161/ATVBAHA.112.300173
80. Leppanen, O., Bjornheden, T., Evaldsson, M., Boren, J., Wiklund, O., and Levin, M. (2006). ATP depletion in macrophages in the core of advanced rabbit atherosclerotic plaques in vivo. Atherosclerosis 188, 323-330. doi: 10.1016/j.atherosclerosis.2005.11.017
81. Levin, M., Leppanen, O., Evaldsson, M., Wiklund, O., Bondjers, G., and Bjornheden, T. (2003). Mapping of ATP, glucose, glycogen, and lactate concentrations within the arterial wall. Arterioscler. Thromb. Vasc. Biol. 23, 1801-1807. doi: 10.1161/01.ATV.0000092872.54026.8D
82. Li, W., Ostblom, M., Xu, L. H., Hellsten, A., Leanderson, P., Liedberg, B., et al. (2006). Cytocidal effects of atheromatous plaque components: the death zone revisited. FASEB J. 20, 2281-2290. doi: 10.1096/fj.06-6114com
83. Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874. doi: 10.1038/nature01323
84. Lipiski, M., Deuel, J., Baek, J. H., Engelsberger, W. R., Buehler, P. W., and Schaer, D. J. (2013). Human phenotype specific haptoglobin therapeutics are both effective in vitro and in vivo to attenuate hemoglobin toxicity in guinea pigs. Antioxid. Redox Signal. doi: 10.1089/ars.2012.5089
85. Lusis, A. J. (2000). Atherosclerosis. Nature 407, 233-241. doi: 10.1038/35025203
86. Luttun, A., Tjwa, M., Moons, L., Wu, Y., Angelillo-Scherrer, A., Liao, F., et al. (2002). Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat. Med. 8, 831-840. doi: 10.1038/nm731
87. Matzinger, P. (1994). Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12, 991-1045. doi: 10.1146/annurev.iy.12.040194.005015
88. Matzinger, P. (2002). The danger model: a renewed sense of self. Science 296, 301-305. doi: 10.1126/science.1071059
89. Maxwell, P. H., Wiesener, M. S., Chang, G. W., Clifford, S. C., Vaux, E. C., Cockman, M. E., et al. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271-275. doi: 10.1038/20459
90. McCarthy, M. J., Loftus, I. M., Thompson, M. M., Jones, L., London, N. J., Bell, P. R., et al. (1999). Angiogenesis and the atherosclerotic carotid plaque: an association between symptomatology and plaque morphology. J. Vasc. Surg. 30, 261-268. doi: 10.1016/S0741-5214(99)70136-9
91. Melamed-Frank, M., Lache, O., Enav, B. I., Szafranek, T., Levy, N. S., Ricklis, R. M., et al. (2001). Structure-function analysis of the antioxidant properties of haptoglobin. Blood 98, 3693-3698. doi: 10.1182/blood.V98.13.3693
92. Michel, J. B., Virmani, R., Arbustini, E., and Pasterkamp, G. (2011). Intraplaque haemorrhages as the trigger of plaque vulnerability. Eur. Heart J. 32, 1977-1985, 1985a, 1985b, 1985c. doi: 10.1093/eurheartj/ehr054
93. Miller, Y. I., Altamentova, S. M., and Shaklai, N. (1997). Oxidation of low-density lipoprotein by hemoglobin stems from a heme-initiated globin radical: antioxidant role of haptoglobin. Biochemistry 36, 12189-12198. doi: 10.1021/bi970258a
94. Moreno, P. R., Purushothaman, K. R., Fuster, V., Echeverri, D., Truszczynska, H., Sharma, S. K., et al. (2004). Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 110, 2032-2038. doi: 10.1161/01.CIR.0000143233.87854.23
95. Moreno, P. R., Purushothaman, K. R., Sirol, M., Levy, A. P., and Fuster, V. (2006). Neovascularization in human atherosclerosis. Circulation 113, 2245-2252. doi: 10.1161/CIRCULATIONAHA.105.578955
96. Moreno, P. R., Purushothaman, M., and Purushothaman, K. R. (2012). Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann. N.Y. Acad. Sci. 1254, 7-17. doi: 10.1111/j.1749-6632.2012.06497.x
97. Moulton, K. S., Heller, E., Konerding, M. A., Flynn, E., Palinski, W., and Folkman, J. (1999). Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99, 1726-1732. doi: 10.1161/01.CIR.99.13.1726
98. Moulton, K. S., Vakili, K., Zurakowski, D., Soliman, M., Butterfield, C., Sylvin, E., et al. (2003). Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc. Natl. Acad. Sci. U.S.A. 100, 4736-4741. doi: 10.1073/pnas.0730843100
99. Nagy, E., Eaton, J. W., Jeney, V., Soares, M. P., Varga, Z., Galajda, Z., et al. (2010). Red cells, hemoglobin, heme, iron, and atherogenesis. Arterioscler. Thromb. Vasc. Biol. 30, 1347-1353. doi: 10.1161/ATVBAHA.110.206433
100. Nagy, E., Jeney, V., Yachie, A., Szabo, R. P., Wagner, O., Vercellotti, G. M., et al. (2005). Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency. Cell. Mol. Biol. (Noisy-le-grand). 51, 377-385. doi: 10.1170/T641
101. Nakano, D., Hayashi, T., Tazawa, N., Yamashita, C., Inamoto, S., Okuda, N., et al. (2005). Chronic hypoxia accelerates the progression of atherosclerosis in apolipoprotein E-knockout mice. Hypertens. Res. 28, 837-845. doi: 10.1291/hypres.28.837
102. Nath, K. A., Balla, G., Vercellotti, G. M., Balla, J., Jacob, H. S., Levitt, M. D., et al. (1992). Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J. Clin. Invest. 90, 267-270. doi: 10.1172/JCI115847
103. O'Brien, E. R., Garvin, M. R., Dev, R., Stewart, D. K., Hinohara, T., Simpson, J. B., et al. (1994). Angiogenesis in human coronary atherosclerotic plaques. Am. J. Pathol. 145, 883-894.
104. Olsson, M. G., Allhorn, M., Larsson, J., Cederlund, M., Lundqvist, K., Schmidtchen, A., et al. (2011). Up-regulation of A1M/alpha1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage. PLoS ONE 6:e27505. doi: 10.1371/journal.pone.0027505
105. Olsson, M. G., Olofsson, T., Tapper, H., and Akerstrom, B. (2008). The lipocalin alpha1-microglobulin protects erythroid K562 cells against oxidative damage induced by heme and reactive oxygen species. Free Radic. Res. 42, 725-736. doi: 10.1080/10715760802337265
106. Pang, J. H., Jiang, M. J., Chen, Y. L., Wang, F. W., Wang, D. L., Chu, S. H., et al. (1996). Increased ferritin gene expression in atherosclerotic lesions. J. Clin. Invest. 97, 2204-2212. doi: 10.1172/JCI118661
107. Paone, A., Galli, R., Gabellini, C., Lukashev, D., Starace, D., Gorlach, A., et al. (2010). Toll-like receptor 3 regulates angiogenesis and apoptosis in prostate cancer cell lines through hypoxia-inducible factor 1 alpha. Neoplasia 12, 539-549. doi: 10.1593/neo.92106
108. Patel, R. P., Svistunenko, D. A., Darley-Usmar, V. M., Symons, M. C., and Wilson, M. T. (1996). Redox cycling of human methaemoglobin by H2O2 yields persistent ferryl iron and protein based radicals. Free Radic. Res. 25, 117-123. doi: 10.3109/10715769609149916
109. Petrovan, R. J., Kaplan, C. D., Reisfeld, R. A., and Curtiss, L. K. (2007). DNA vaccination against VEGF receptor 2 reduces atherosclerosis in LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 27, 1095-1100. doi: 10.1161/ATVBAHA.106.139246
110. Pimenova, T., Pereira, C. P., Gehrig, P., Buehler, P. W., Schaer, D. J., and Zenobi, R. (2010). Quantitative mass spectrometry defines an oxidative hotspot in hemoglobin that is specifically protected by haptoglobin. J. Proteome Res. 9, 4061-4070. doi: 10.1021/pr100252e
111. Pollet, I., Opina, C. J., Zimmerman, C., Leong, K. G., Wong, F., and Karsan, A. (2003). Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-kappaB and c-Jun N-terminal kinase. Blood 102, 1740-1742. doi: 10.1182/blood-2003-01-0288
112. Porto, B. N., Alves, L. S., Fernandez, P. L., Dutra, T. P., Figueiredo, R. T., Graca-Souza, A. V., et al. (2007). Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors. J. Biol. Chem. 282, 24430-24436. doi: 10.1074/jbc.M703570200
113. Potor, L., Banyai, E., Becs, G., Soares, M. P., Balla, G., Balla, J., et al. (2013). Atherogenesis may involve the prooxidant and proinflammatory effects of ferryl hemoglobin. Oxid. Med. Cell. Longev. 2013:676425. doi: 10.1155/2013/676425
114. Radhakrishnan, N., Yadav, S. P., Sachdeva, A., Pruthi, P. K., Sawhney, S., Piplani, T., et al. (2011). Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and asplenia. J. Pediatr. Hematol. Oncol. 33, 74-78. doi: 10.1097/MPH.0b013e3181fd2aae
115. Rajamaki, K., Lappalainen, J., Oorni, K., Valimaki, E., Matikainen, S., Kovanen, P. T., et al. (2010). Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS ONE 5:e11765. doi: 10.1371/journal.pone.0011765
116. Ramirez, D. C., Chen, Y. R., and Mason, R. P. (2003). Immunochemical detection of hemoglobin-derived radicals formed by reaction with hydrogen peroxide: involvement of a protein-tyrosyl radical. Free Radic. Biol. Med. 34, 830-839. doi: 10.1016/S0891-5849(02)01437-5
117. Reeder, B. J., Cutruzzola, F., Bigotti, M. G., Hider, R. C., and Wilson, M. T. (2008). Tyrosine as a redox-active center in electron transfer to ferryl heme in globins. Free Radic. Biol. Med. 44, 274-283. doi: 10.1016/j.freeradbiomed.2007.06.030
118. Ritman, E. L., and Lerman, A. (2007). The dynamic vasa vasorum. Cardiovasc. Res. 75, 649-658. doi: 10.1016/j.cardiores.2007.06.020
119. Sahebkar, A., and Watts, G. F. (2013). New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes. Clin. Ther. 35, 1082-1098. doi: 10.1016/j.clinthera.2013.06.019
120. Schaer, C. A., Deuel, J. W., Bittermann, A. G., Rubio, I. G., Schoedon, G., Spahn, D. R., et al. (2013b). Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage. Cell Death Differ. 20, 1569-1579. doi: 10.1038/cdd.2013.113
121. Schaer, D. J., Buehler, P. W., Alayash, A. I., Belcher, J. D., and Vercellotti, G. M. (2013a). Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood 121, 1276-1284. doi: 10.1182/blood-2012-11-451229
122. Schaer, D. J., Schaer, C. A., Buehler, P. W., Boykins, R. A., Schoedon, G., Alayash, A. I., et al. (2006). CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood 107, 373-380. doi: 10.1182/blood-2005-03-1014
123. Siems, W. G., Sommerburg, O., and Grune, T. (2000). Erythrocyte free radical and energy metabolism. Clin. Nephrol. 53, S9-S17.
124. Silva, G., Jeney, V., Chora, A., Larsen, R., Balla, J., and Soares, M. P. (2009). Oxidized hemoglobin is an endogenous proinflammatory agonist that targets vascular endothelial cells. J. Biol. Chem. 284, 29582-29595. doi: 10.1074/jbc.M109.045344
125. Sluimer, J. C., Gasc, J. M., van Wanroij, J. L., Kisters, N., Groeneweg, M., Sollewijn Gelpke, M. D., et al. (2008). Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. J. Am. Coll. Cardiol. 51, 1258-1265. doi: 10.1016/j.jacc.2007.12.025
126. Sluimer, J. C., Kolodgie, F. D., Bijnens, A. P., Maxfield, K., Pacheco, E., Kutys, B., et al. (2009). Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J. Am. Coll. Cardiol. 53, 1517-1527. doi: 10.1016/j.jacc.2008.12.056
127. Spirig, R., Djafarzadeh, S., Regueira, T., Shaw, S. G., von Garnier, C., Takala, J., et al. (2010). Effects of TLR agonists on the hypoxia-regulated transcription factor HIF-1alpha and dendritic cell maturation under normoxic conditions. PLoS ONE 5:e0010983. doi: 10.1371/journal.pone.0010983
128. Sverrisson, K., Axelsson, J., Rippe, A., Gram, M., Akerstrom, B., Hansson, S. R., et al. (2014). Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with alpha1-microglobulin and tempol. Am. J. Physiol. Renal Physiol. 306, F442-F448. doi: 10.1152/ajprenal.00502.2013
129. Tenhunen, R., Marver, H. S., and Schmid, R. (1968). The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. U.S.A. 61, 748-755. doi: 10.1073/pnas.61.2.748
130. Torres Filho, I. P., Leunig, M., Yuan, F., Intaglietta, M., and Jain, R. K. (1994). Noninvasive measurement of microvascular and interstitial oxygen profiles in a human tumor in SCID mice. Proc. Natl. Acad. Sci. U.S.A. 91, 2081-2085. doi: 10.1073/pnas.91.6.2081
131. Tynan, M. B., Nicholls, D. P., Maguire, S. M., Steele, I. C., McMaster, C., Moore, R., et al. (1995). Erythrocyte membrane fatty acid composition as a marker of dietary compliance in hyperlipidaemic subjects. Atherosclerosis 117, 245-252. doi: 10.1016/0021-9150(95)05578-K
132. Tziakas, D., Chalikias, G., Kapelouzou, A., Tentes, I., Schafer, K., Karayannakos, P., et al. (2013). Erythrocyte membrane cholesterol and lipid core growth in a rabbit model of atherosclerosis: modulatory effects of rosuvastatin. Int. J. Cardiol. 170, 173-181. doi: 10.1016/j.ijcard.2013.10.070
133. Vallelian, F., Pimenova, T., Pereira, C. P., Abraham, B., Mikolajczyk, M. G., Schoedon, G., et al. (2008). The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways. Free Radic. Biol. Med. 45, 1150-1158. doi: 10.1016/j.freeradbiomed.2008.07.013
134. Vincent, S. H., Grady, R. W., Shaklai, N., Snider, J. M., and Muller-Eberhard, U. (1988). The influence of heme-binding proteins in heme-catalyzed oxidations. Arch. Biochem. Biophys. 265, 539-550. doi: 10.1016/0003-9861(88)90159-2
135. Vinchi, F., De Franceschi, L., Ghigo, A., Townes, T., Cimino, J., Silengo, L., et al. (2013). Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation 127, 1317-1329. doi: 10.1161/CIRCULATIONAHA.112.130179
136. Vinchi, F., Muckenthaler, M. U., Da Silva, M. C., Balla, G., Balla, J., and Jeney, V. (2014). Atherogenesis and iron: from epidemiology to cellular level. Front. Pharmacol. 5:94. doi: 10.3389/fphar.2014.00094
137. Vink, A., Schoneveld, A. H., Lamers, D., Houben, A. J., van der Groep, P., van Diest, P. J., et al. (2007). HIF-1 alpha expression is associated with an atheromatous inflammatory plaque phenotype and upregulated in activated macrophages. Atherosclerosis 195, e69-e75. doi: 10.1016/j.atherosclerosis.2007.05.026
138. Wagener, F. A., Eggert, A., Boerman, O. C., Oyen, W. J., Verhofstad, A., Abraham, N. G., et al. (2001). Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase. Blood 98, 1802-1811. doi: 10.1182/blood.V98.6.1802
139. Wagener, F. A., Feldman, E., de Witte, T., and Abraham, N. G. (1997). Heme induces the expression of adhesion molecules ICAM-1, VCAM-1, and E selectin in vascular endothelial cells. Proc. Soc. Exp. Biol. Med. 216, 456-463. doi: 10.3181/00379727-216-44197
140. Wang, G. L., Jiang, B. H., Rue, E. A., and Semenza, G. L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. U.S.A. 92, 5510-5514. doi: 10.1073/pnas.92.12.5510
141. Wang, G. L., and Semenza, G. L. (1995). Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 270, 1230-1237. doi: 10.1074/jbc.270.3.1230
142. Wenger, R. H., Stiehl, D. P., and Camenisch, G. (2005). Integration of oxygen signaling at the consensus HRE. Sci. STKE 2005:re12. doi: 10.1126/stke.3062005re12
143. West, X. Z., Malinin, N. L., Merkulova, A. A., Tischenko, M., Kerr, B. A., Borden, E. C., et al. (2010). Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 467, 972-976. doi: 10.1038/nature09421
144. Yachie, A., Niida, Y., Wada, T., Igarashi, N., Kaneda, H., Toma, T., et al. (1999). Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest. 103, 129-135. doi: 10.1172/JCI4165
145. Yeagle, P. L. (1985). Cholesterol and the cell membrane. Biochim. Biophys. Acta 822, 267-287. doi: 10.1016/0304-4157(85)90011-5
146. Yet, S. F., Layne, M. D., Liu, X., Chen, Y. H., Ith, B., Sibinga, N. E., et al. (2003). Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling. FASEB J. 17, 1759-1761. doi: 10.1096/fj.03-0187fje
147. Zarjou, A., Jeney, V., Arosio, P., Poli, M., Antal-Szalmas, P., Agarwal, A., et al. (2009). Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells. J. Am. Soc. Nephrol. 20, 1254-1263. doi: 10.1681/ASN.2008070788
148. Zemplenyi, T., Crawford, D. W., and Cole, M. A. (1989). Adaptation to arterial wall hypoxia demonstrated in vivo with oxygen microcathodes. Atherosclerosis 76, 173-179. doi: 10.1016/0021-9150(89)90101-9
149. Zhang, Y., Cliff, W. J., Schoefl, G. I., and Higgins, G. (1993). Immunohistochemical study of intimal microvessels in coronary atherosclerosis. Am. J. Pathol. 143, 164-172.