Atherosclerosis as a paradigmatic disease of the elderly: role of the immune system.
When a new hypothesis about the etiology and pathogenesis of a disease is developed, there is always the danger that it will be presented as the only acceptable explanation for the occurrence of a given pathologic condition. In view of the well-proven multifactoral pathogenesis of atherosclerosis, we would like to emphasize that we are not postulating that immunity to HSP60 is the only cause of atherogenesis, especially in the later stages where there are clinically-apparent sequelae, such as myocardial infarction, stroke, and other atherosclerosis-dependent symptoms. In this article, we summarized some of the experimental and clinical data that we and others have collected in support of the concept that atherosclerosis is a good example of pleotropic antagonism, and postulated that age-dependent diseases are the price we pay for genetic traits established by natural selection to assure maximum survival until the age of reproduction, the effects of which may, however, become deleterious later in life. In the present case, the cost we pay for protective immunity to microbial and altered autologous HSP60 is the risk of cross-reactivity with HSP60 expressed by arterial endothelial cells that are subjected to stress factors already known as classical atherosclerosis risk factors. We showed that the first inflammatory stage of atherosclerosis starts early in life, long before it becomes clinically apparent. More severe lesions that lead to atherosclerosis-dependent organ-specific or systemic symptoms will only occur if classical atherosclerosis risk factors, especially those involving the cholesterol metabolism, remain present.
Knoflach
Michael
M
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
Mayrl
Bruno
B
Mayerl
Christina
C
Sedivy
Roland
R
Wick
Georg
G
D000368:Aged; D000375:Aging / Q000276:immunology*; D001161:Arteriosclerosis / Q000276:immunology*; D015551:Autoimmunity; D018834:Chaperonin 60 / Q000276:immunology*; D006801:Humans
D018834:Chaperonin 60