The autoimmune concept of atherosclerosis

Curr Opin Lipidol. 2011 Oct;22(5):327-34. doi: 10.1097/MOL.0b013e32834aa0c2.


Purpose of review: This review summarizes the recent data on the 'Autoimmune Concept of Atherosclerosis', according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors.

Recent findings: Plasma cholesterol and LDL levels considered 'normal' by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in 'normocholesterolemic' individuals.

Summary: We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / blood*
  • Atherosclerosis / immunology*
  • Autoimmunity / immunology*
  • Chaperonin 60 / immunology
  • Cholesterol / blood
  • Humans
  • Lipoproteins, LDL / blood
  • Risk Factors


  • Chaperonin 60
  • Lipoproteins, LDL
  • Cholesterol