The role of heat shock proteins in atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Medicine
• Pathogenesis of Atherosclerosis

Background:

• Atherosclerosis is a chronic, inflammatory disease initiating in youth and leading to severe cardiovascular events.
• Inflammation's role in atherogenesis has gained significant attention in recent decades.
• Early atherosclerotic lesions show T cell infiltration at arterial sites, recognizing heat shock protein 60 (HSP60).

Purpose of the Study:

• To investigate the role of T cells and antibodies targeting heat shock protein 60 (HSP60) in atherosclerosis development.
• To explore the potential link between immunity to microbial HSP60 and the pathogenesis of atherosclerosis.

Main Methods:

• Analysis of early atherosclerotic lesions in animal models and humans.
• Identification of T cell recognition targets within the arterial intima.
• Examination of endothelial cell expression of HSP60 and adhesion molecules in response to risk factors.

Main Results:

• T cells recognizing HSP60 are the initial pathogenic event in atherogenesis.
• Endothelial cells express HSP60 and adhesion molecules under stress from atherosclerosis risk factors.
• Antibodies against HSP60 exacerbate and sustain the atherosclerotic disease process.

Conclusions:

• Atherosclerosis may arise from the immune system's response to HSP60, particularly microbial HSP60 due to sequence homology with human HSP60.
• The body's protective immunity against microbial HSP60 could inadvertently promote atherosclerosis under conditions of vascular stress.
• This suggests a potential trade-off between immunity to pathogens and the risk of developing atherosclerosis.