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November 17, 2004

Role of Toll-like Receptor 4 in Acute Myocardial Infarction and Longevity

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2004;292(19):2335-2340. doi:10.1001/jama.292.19.2339

To the Editor: A major trait characterizing centenarians is a relatively low frequency of cardiovascular disease (CVD). Since a proinflammatory genotype appears to contribute to the risk of ischemic heart disease, the prevalence of proinflammatory alleles would also be expected to be relatively low in people experiencing longevity.1 Toll-like receptor 4 (TLR4), the activity of which may be modulated by genetic polymorphisms, is a signaling receptor in innate immune defense. It is activated by lipopolysaccharide from gram-negative bacteria and endogenous ligands, including those produced in response to tissue injury. TLR4 is expressed on virtually all cells. However, in atherosclerotic tissue its expression is markedly up-regulated, and the inflammatory mediators produced by its activation exert various atherogenic effects.2,3 In this study, we evaluated whether prevalence of the TLR4 genotype may have an association with acute myocardial infarction (AMI) and with longevity.

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