Table of Contents Author Guidelines Submit a Manuscript
Autoimmune Diseases
Volume 2012, Article ID 502813, 9 pages
http://dx.doi.org/10.1155/2012/502813
Review Article

Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

Division of Cardiac Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21287, USA

Received 15 June 2012; Revised 15 September 2012; Accepted 24 September 2012

Academic Editor: Boel De Paepe

Copyright © 2012 Arman Kilic and Kaushik Mandal. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Milkman, “Temperature effects on day old Drosophila pupae,” The Journal of General Physiology, vol. 45, pp. 777–799, 1962. View at Google Scholar · View at Scopus
  2. R. I. Morimoto, “Cells in stress: transcriptional activation of heat shock genes,” Science, vol. 259, no. 5100, pp. 1409–1410, 1993. View at Google Scholar · View at Scopus
  3. J. Madrigal-Matute, J. L. Martin-Ventura, L. M. Blanco-Colio, J. Egido, J. B. Michel, and O. Meilhac, “Heat-shock proteins in cardiovascular disease,” Advances in Clinical Chemistry, vol. 54, pp. 1–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. Q. Xu, B. Metzler, M. Jahangiri, and K. Mandal, “Molecular chaperones and heat shock proteins in atherosclerosis,” American Journal of Physiology, vol. 302, no. 3, pp. H506–H514, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Bielecka-Dabrowa, M. Barylski, D. P. Mikhailidis, J. Rysz, and M. Banach, “HSP 70 and atherosclerosis—protector or activator?” Expert Opinion on Therapeutic Targets, vol. 13, no. 3, pp. 307–317, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. Q. Xu, “Biomechanical-stress-induced signaling and gene expression in the development of arteriosclerosis,” Trends in Cardiovascular Medicine, vol. 10, no. 1, pp. 35–41, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. F. U. Hartl, “Heat shock proteins in protein folding and membrane translocation,” Seminars in Immunology, vol. 3, no. 1, pp. 5–16, 1991. View at Google Scholar · View at Scopus
  8. P. Roma and A. L. Catapano, “Stress proteins and atherosclerosis,” Atherosclerosis, vol. 127, no. 2, pp. 147–154, 1996. View at Publisher · View at Google Scholar · View at Scopus
  9. K. L. Nielsen and N. J. Cowan, “A single ring is sufficient for productive chaperonin-mediated folding in vivo,” Molecular Cell, vol. 2, no. 1, pp. 93–99, 1998. View at Google Scholar · View at Scopus
  10. M. R. Voss, J. N. Stallone, M. Li, R. N. M. Cornelussen, P. Knuefermann, and A. A. Knowlton, “Gender differences in the expression of heat shock proteins: the effect of estrogen,” American Journal of Physiology, vol. 285, no. 2, pp. H687–H692, 2003. View at Google Scholar · View at Scopus
  11. K. Rayner, Y. X. Chen, T. Siebert, and E. R. O'Brien, “Heat shock protein 27: clue to understanding estrogen-mediated atheroprotection?” Trends in Cardiovascular Medicine, vol. 20, no. 2, pp. 54–58, 2010. View at Google Scholar · View at Scopus
  12. M. Shimizu, M. Tamamori-Adachi, H. Arai, N. Tabuchi, H. Tanaka, and M. Sunamori, “Lipopolysaccharide pretreatment attenuates myocardial infarct size: a possible mechanism involving heat shock protein 70-inhibitory κBα complex and attenuation of nuclear factor κB,” Journal of Thoracic and Cardiovascular Surgery, vol. 124, no. 5, pp. 933–941, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. W. B. Pratt and D. O. Toft, “Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery,” Experimental Biology and Medicine, vol. 228, no. 2, pp. 111–133, 2003. View at Google Scholar · View at Scopus
  14. G. Wick, G. Schett, A. Amberger, R. Kleindienst, and Q. Xu, “Is atherosclerosis an immunologically mediated disease?” Immunology Today, vol. 16, no. 1, pp. 27–33, 1995. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Giannessi, C. Colotti, M. Maltinti et al., “Circulating heat shock proteins and inflammatory markers in patients with idiopathic left ventricular dysfunction: their relationships with myocardial and microvascular impairment,” Cell Stress and Chaperones, vol. 12, no. 3, pp. 265–274, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. R. A. Young and T. J. Elliott, “Stress proteins, infection, and immune surveillance,” Cell, vol. 59, no. 1, pp. 5–8, 1989. View at Google Scholar · View at Scopus
  17. G. Wick, R. Kleindienst, G. Schett, A. Amberger, and Q. Xu, “Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis,” International Archives of Allergy and Immunology, vol. 107, no. 1–3, pp. 130–131, 1995. View at Google Scholar · View at Scopus
  18. A. Amberger, C. Maczek, G. Jürgens et al., “Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins,” Cell Stress and Chaperones, vol. 2, no. 2, pp. 94–103, 1997. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Kol, T. Bourcier, A. H. Lichtman, and P. Libby, “Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages,” The Journal of Clinical Investigation, vol. 103, no. 4, pp. 571–577, 1999. View at Google Scholar · View at Scopus
  20. A. Rossmann, B. Henderson, B. Heidecker et al., “T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire,” Experimental Gerontology, vol. 43, no. 3, pp. 229–237, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Knoflach, S. Kiechl, M. Kind et al., “Cardiovascular risk factors and atherosclerosis in young males: ARMY study (atherosclerosis risk-factors in male youngsters),” Circulation, vol. 108, no. 9, pp. 1064–1069, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. A. S. Major, S. Fazio, and M. F. Linton, “B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 11, pp. 1892–1898, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. G. Caligiuri, A. Nicoletti, B. Poirierand, and G. K. Hansson, “Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice,” The Journal of Clinical Investigation, vol. 109, no. 6, pp. 745–753, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Kyaw, C. Tay, A. Khan et al., “Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis,” The Journal of Immunology, vol. 185, no. 7, pp. 4410–4419, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. D. R. Greaves and K. M. Channon, “Inflammation and immune responses in atherosclerosis,” Trends in Immunology, vol. 23, no. 11, pp. 535–541, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. Q. Xu, G. Schett, H. Perschinka et al., “Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population,” Circulation, vol. 102, no. 1, pp. 14–20, 2000. View at Google Scholar · View at Scopus
  27. A. Kol, G. K. Sukhova, A. H. Lichtman, and P. Libby, “Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-α and matrix metalloproteinase expression,” Circulation, vol. 98, no. 4, pp. 300–307, 1998. View at Google Scholar · View at Scopus
  28. B. Dybdahl, S. A. Slørdahl, A. Waage, P. Kierulf, T. Espevik, and A. Sundan, “Myocardial ischaemia and the inflammatory response: release of heat shock protein 70 after myocardial infarction,” Heart, vol. 91, no. 3, pp. 299–304, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. Q. Xiao, K. Mandal, G. Schett et al., “Association of serum-soluble heat shock protein 60 with carotid atherosclerosis: clinical significance determined in a follow-up study,” Stroke, vol. 36, no. 12, pp. 2571–2576, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Satoh, Y. Shimoda, T. Akatsu, Y. Ishikawa, Y. Minami, and M. Nakamura, “Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction,” European Journal of Heart Failure, vol. 8, no. 8, pp. 810–815, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Gombos, Z. Förhécz, Z. Pozsonyi, L. Jánoskuti, and Z. Prohászka, “Interaction of serum 70-kDa heat shock protein levels and HspA1B (+1267) gene polymorphism with disease severity in patients with chronic heart failure,” Cell Stress and Chaperones, vol. 13, no. 2, pp. 199–206, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. X. Zhang, M. He, L. Cheng et al., “Elevated heat shock protein 60 levels are associated with higher risk of coronary heart disease in Chinese,” Circulation, vol. 118, no. 25, pp. 2687–2693, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. Q. Xu, J. Willeit, M. Marosi et al., “Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis,” The Lancet, vol. 341, no. 8840, pp. 255–259, 1993. View at Publisher · View at Google Scholar · View at Scopus
  34. Q. Xu, S. Kiechl, M. Mayr et al., “Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis: clinical significance determined in a follow-up study,” Circulation, vol. 100, no. 11, pp. 1169–1174, 1999. View at Google Scholar · View at Scopus
  35. M. Mayr, S. Kiechl, J. Willeit, G. Wick, and Q. Xu, “Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis,” Circulation, vol. 102, no. 8, pp. 833–839, 2000. View at Google Scholar · View at Scopus
  36. T. Huittinen, M. Leinonen, L. Tenkanen et al., “Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 3, pp. 431–437, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. E. Reszka, B. Jegier, W. Wasowicz, M. Lelonek, M. Banach, and R. Jaszewski, “Detection of infectious agents by polymerase chain reaction in human aortic wall,” Cardiovascular Pathology, vol. 17, no. 5, pp. 297–302, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. G. Foteinos, A. R. Afzal, K. Mandal, M. Jahangiri, and Q. Xu, “Anti-heat shock protein 60 autoantibodies induce atherosclerosis in apolipoprotein E-deficient mice via endothelial damage,” Circulation, vol. 112, no. 8, pp. 1206–1213, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. J. George, A. Afek, B. Gilburd, Y. Shoenfeld, and D. Harats, “Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice,” Journal of the American College of Cardiology, vol. 38, no. 3, pp. 900–905, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. Q. Xu, H. Dietrich, H. J. Steiner et al., “Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65,” Arteriosclerosis and Thrombosis, vol. 12, no. 7, pp. 789–799, 1992. View at Google Scholar · View at Scopus
  41. B. Metzler, M. Mayr, H. Dietrich et al., “Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemic rabbits immunized with heat shock protein 65,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 8, pp. 1905–1911, 1999. View at Google Scholar · View at Scopus
  42. J. J. Hansen, P. Bross, M. Westergaard et al., “Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter,” Human Genetics, vol. 112, no. 1, pp. 71–77, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. X. Shan, T. J. Liu, H. F. Su, A. Samsamshariat, R. Mestril, and P. H. Wang, “Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells,” Journal of Molecular and Cellular Cardiology, vol. 35, no. 9, pp. 1135–1143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Z. Badrichani, D. M. Stroka, G. Bilbao, D. T. Curiel, F. H. Bach, and C. Ferran, “Bcl-2 and Bcl-X(L) serve an anti-inflammatory function in endothelial cells through inhibition of NF-κB,” The Journal of Clinical Investigation, vol. 103, no. 4, pp. 543–553, 1999. View at Google Scholar · View at Scopus
  45. A. Ciervo, A. Petrucca, U. Villano, G. Fioroni, and A. Cassone, “Low prevalence of antibodies against heat shock protein 10 of Chlamydophila pneumoniae in patients with coronary heart disease,” Journal of Microbiological Methods, vol. 63, no. 3, pp. 248–253, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. H. K. Park, E. C. Park, S. W. Bae et al., “Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome,” Circulation, vol. 114, no. 9, pp. 886–893, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. J. L. Martin-Ventura, M. C. Duran, L. M. Blanco-Colio et al., “Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis,” Circulation, vol. 110, no. 15, pp. 2216–2219, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. A. I. De Souza, R. Wait, A. G. Mitchell, N. R. Banner, M. J. Dunn, and M. L. Rose, “Heat shock protein 27 is associated with freedom from graft vasculopathy after human cardiac transplantation,” Circulation Research, vol. 97, no. 2, pp. 192–198, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. H. R. Lijnen, “Plasmin and matrix metalloproteinases in vascular remodeling,” Thrombosis and Haemostasis, vol. 86, no. 1, pp. 324–333, 2001. View at Google Scholar · View at Scopus
  50. A. J. Lepedda, A. Cigliano, G. M. Cherchi et al., “A proteomic approach to differentiate histologically classified stable and unstable plaques from human carotid arteries,” Atherosclerosis, vol. 203, no. 1, pp. 112–118, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Guay, H. Lambert, G. Gingras-Breton, J. N. Lavoie, J. Huot, and J. Landry, “Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27,” Journal of Cell Science, vol. 110, no. 3, pp. 357–368, 1997. View at Google Scholar · View at Scopus
  52. J. L. Martin-Ventura, V. Nicolas, X. Houard et al., “Biological significance of decreased HSP27 in human atherosclerosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 6, pp. 1337–1343, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Rayner, Y. X. Chen, M. McNulty et al., “Extracellular release of the atheroprotective heat shock protein 27 is mediated by estrogen and competitively inhibits acLDL binding to scavenger receptor-a,” Circulation Research, vol. 103, no. 2, pp. 133–141, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Miller, S. Poon, B. Hibbert, K. Rayner, Y. X. Chen, and E. R. O'Brien, “Modulation of estrogen signaling by the novel interaction of heat shock protein 27, a biomarker for atherosclerosis, and estrogen receptor beta: mechanistic insight into the vascular effects of estrogens,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 3, pp. e10–e14, 2005. View at Google Scholar · View at Scopus
  55. P. Y. Liu, R. C. Christian, M. Ruan, V. M. Miller, and L. A. Fitzpatrick, “Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 2, pp. 1041–1046, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. R. C. Christian, P. Y. Liu, S. Harrington, M. Ruan, V. M. Miller, and L. A. Fitzpatrick, “Intimal estrogen Receptor (ER)β, but Not ERα expression, is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 7, pp. 2713–2720, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. V. Bobryshev and R. S. A. Lord, “Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis,” Journal of Vascular Surgery, vol. 35, no. 2, pp. 368–375, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. Z. Han, Q. A. Truong, S. Park, and J. L. Breslow, “Two Hsp70 family members expressed in atherosclerotic lesions,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 1256–1261, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. P. A. Svensson, A. Asea, M. C. O. Englund et al., “Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages,” Atherosclerosis, vol. 185, no. 1, pp. 32–38, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. U. Wendling, L. Paul, R. Van Der Zee, B. Prakken, M. Singh, and W. Van Eden, “A conserved mycobacterial heat shock protein (hsp) 70 sequence prevents adjuvant arthritis upon nasal administration and induces IL-10-producing T cells that cross-react with the mammalian self-hsp70 homologue,” The Journal of Immunology, vol. 164, no. 5, pp. 2711–2717, 2000. View at Google Scholar · View at Scopus
  61. M. Shimizu, M. Tamamori-Adachi, H. Arai, N. Tabuchi, H. Tanaka, and M. Sunamori, “Lipopolysaccharide pretreatment attenuates myocardial infarct size: a possible mechanism involving heat shock protein 70-inhibitory κBα complex and attenuation of nuclear factor κB,” Journal of Thoracic and Cardiovascular Surgery, vol. 124, no. 5, pp. 933–941, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Zhu, A. A. Quyyumi, H. Wu et al., “Increased serum levels of heat shock protein 70 are associated with low risk of coronary artery disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 6, pp. 1055–1059, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. J. L. Martin-Ventura, A. Leclercq, L. M. Blanco-Colio et al., “Low plasma levels of HSP70 in patients with carotid atherosclerosis are associated with increased levels of proteolytic markers of neutrophil activation,” Atherosclerosis, vol. 194, no. 2, pp. 334–341, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Yao, A. D. Watson, S. Ji, and K. I. Boström, “Heat shock protein 70 enhances vascular bone morphogenetic protein-4 signaling by binding Matrix Gla protein,” Circulation Research, vol. 105, no. 6, pp. 575–584, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Businaro, E. Profumo, A. Tagliani et al., “Heat-shock protein 90: a novel autoantigen in human carotid atherosclerosis,” Atherosclerosis, vol. 207, no. 1, pp. 74–83, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Madrigal-Matute, O. López-Franco, L. M. Blanco-Colio et al., “Heat shock protein 90 inhibitors attenuate inflammatory responses in atherosclerosis,” Cardiovascular Research, vol. 86, no. 2, pp. 330–337, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. J. Madrigal-Matute, C. E. Fernandez-Garcia, C. Gomez-Guerrero et al., “HSP90 inhibition by 17-DMAG attenuates oxidative stress in experimental atherosclerosis,” Cardiovascular Research, vol. 95, no. 1, pp. 116–123, 2012. View at Publisher · View at Google Scholar · View at Scopus
  68. S. K. Shimp III, C. B. Chafin, N. L. Regna et al., “Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus,” Cellular and Molecular Immunology, vol. 9, no. 3, pp. 255–266, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Chatterjee, C. Dimitropoulou, F. Drakopanayiotakis et al., “Heat shock protein 90 inhibitors prolong survival, attenuate inflammation, and reduce lung injury in murine sepsis,” American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 7, pp. 667–675, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. D. H. Birnie, E. R. Holme, I. C. McKay, S. Hood, K. E. L. McColl, and W. S. Hillis, “Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk,” European Heart Journal, vol. 19, no. 3, pp. 387–394, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Barylski, J. Małyszko, J. Rysz, M. Myśliwiec, and M. Banach, “Lipids, blood pressure, kidney—what was new in 2011?” Archives of Medical Science, vol. 7, no. 6, pp. 1055–1066, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. F. Hoppichler, T. Koch, A. Dzien, G. Gschwandtner, and M. Lechleitner, “Prognostic value of antibody titre to heat-shock protein 65 on cardiovascular events,” Cardiology, vol. 94, no. 4, pp. 220–223, 2000. View at Publisher · View at Google Scholar · View at Scopus
  73. D. H. Birnie, L. E. Vickers, W. S. Hillis, J. Norrie, and S. M. Cobbe, “Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain,” Heart, vol. 91, no. 9, pp. 1148–1153, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. R. Maron, G. Sukhova, A. M. Faria et al., “Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice,” Circulation, vol. 106, no. 13, pp. 1708–1715, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. D. Harats, N. Yacov, B. Gilburd, Y. Shoenfeld, and J. George, “Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions,” Journal of the American College of Cardiology, vol. 40, no. 7, pp. 1333–1338, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. L. Pilla, R. Patuzzo, L. Rivoltini et al., “A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-α in metastatic melanoma patients,” Cancer Immunology, Immunotherapy, vol. 55, no. 8, pp. 958–968, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. L. Jun, L. Jie, Y. Dongping et al., “Effects of nasal immunization of multi-target preventive vaccines on atherosclerosis,” Vaccine, vol. 30, no. 6, pp. 1029–1037, 2012. View at Publisher · View at Google Scholar · View at Scopus
  78. C. Keijzer, L. Wieten, M. Van Herwijnen, R. Van Der Zee, W. Van Eden, and F. Broere, “Heat shock proteins are therapeutic targets in autoimmune diseases and other chronic inflammatory conditions,” Expert Opinion on Therapeutic Targets, vol. 16, no. 9, pp. 849–857, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Ugurlucan, D. Erer, Y. Kalko et al., “Aortic stiffness in diabetes mellitus—association with glutamine and heat shock protein 70 expression: a pilot study based on an experimental rodent model,” Expert Opinion on Therapeutic Targets, vol. 13, no. 3, pp. 267–274, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Ishii, T. Seike, T. Nakashima et al., “Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib,” Blood Cancer Journal, vol. 2, no. 4, e68, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Kaiser, A. Kühnl, J. Reins et al., “Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia,” Blood Cancer Journal, vol. 1, article e28, 2011. View at Google Scholar
  82. Y. Bernard, N. Ribeiro, F. Thuaud et al., “Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27,” PLoS ONE, vol. 6, no. 10, Article ID e25302, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. O. Selimoglu, M. Ugurlucan, M. Basaran et al., “Efficacy of remote ischaemic preconditioning for spinal cord protection against ischaemic injury: association with heat shock protein expression,” Folia Neuropathologica, vol. 46, no. 3, pp. 204–212, 2008. View at Google Scholar · View at Scopus