Tolerization against atherosclerosis using heat shock protein 60

Cell Stress Chaperones. 2016 Mar;21(2):201-11. doi: 10.1007/s12192-015-0659-z. Epub 2015 Nov 17.


Atherosclerosis is a chronic inflammatory disease of the artery wall, and both innate and adaptive immunity play important roles in the pathogenesis of this disease. In several experimental and human experiments of early atherosclerotic lesions, it has been shown that the first pathogenic event in atherogenesis is intimal infiltration of T cells at predilection sites. These T cells react to heat shock protein 60 (HSP60), which is a ubiquitous self-antigen expressed on the surface of endothelial cells (ECs) together with adhesion molecules in response to classical risk factors for atherosclerosis. When HSP60 is expressed on the EC surface, it can act as a "danger-signal" for both cellular and humoral immune reactions. Acquired by infection or vaccination, beneficial protective immunity to microbial HSP60 and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. Thus, the development of atherosclerosis during aging is paid by the price for lifelong protective preexisting anti-HSP60 immunity by harmful (auto)immune cross-reactive attack on arterial ECs maltreated by atherosclerosis risk factors. This is supported by experiments, which shows that bacterial HSP60 immunization can lead and accelerate experimental atherosclerosis. This review article presents accumulating proof that supports the idea that tolerization with antigenic HSP60 protein or its peptides may arrest or even prevent atherosclerosis by increased production of regulatory T cells and/or anti-inflammatory cytokines. Recent data indicates that HSP60, or more likely some of its derivative peptides, has immunoregulatory functions. Therefore, these peptides may have important potential for being used as diagnostic agents or therapeutic targets.

Keywords: Atherosclerosis; Heat shock protein 60; Peptides; Therapy; Tolerization.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / immunology*
  • Atherosclerosis / microbiology*
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control
  • Autoimmunity*
  • Bacteria / immunology
  • Bacterial Infections / complications
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology
  • Bacterial Proteins / immunology
  • Chaperonin 60 / immunology*
  • Cytokines / immunology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / microbiology
  • Endothelium, Vascular / pathology
  • Humans
  • Immune Tolerance
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / microbiology
  • T-Lymphocytes, Regulatory / pathology


  • Bacterial Proteins
  • Chaperonin 60
  • Cytokines