Autoimmunity to heat shock proteins in atherosclerosis.
Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of atherosclerosis. It has been observed that most human beings have cellular and humoral reactions against microbial heat shock protein (HSP). Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to HSPs have been demonstrated within atherosclerotic plaques. Most of the known risk factors for atherosclerosis, viz. oxidized low-density lipoprotein, hypertension, infections and oxidative stress, evoke increased expression of HSPs in endothelial cells, smooth muscle cells and macrophages, the main cellular constituents of atherosclerotic plaques. Evolutionary conservation has resulted in a high degree of sequence homology between microbial and human HSPs and hence the immune reactions against microbial HSPs carry a risk of being misdirected towards human HSPs expressed in the stressed cells of the blood vessels. HSPs and anti-HSP antibodies have been shown to elicit production of pro-inflammatory cytokines by macrophages and adhesion molecules by endothelial cells in various in vitro and animal model studies. These autoimmune reactions to HSPs expressed in the vascular tissue can contribute to both initiation and perpetuation of atherosclerosis.
Mandal
Kaushik
K
Department of Cardiothoracic Surgery and Cardiological Sciences, St. George's Hospital and Medical School, Cranmer Terrace, London SW17 0RE, UK.
Jahangiri
Marjan
M
Xu
Qingbo
Q
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
D001426:Bacterial Proteins; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins