doi: 10.1161/01.RES.0000144806.19585.5b
© 2004 American Heart Association, Inc.
Editorial |
Toll Gates and Traffic Arteries
From Endothelial TLR2 to Atherosclerosis
From the Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada.
Correspondence to Paul Kubes, PhD, Dept of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail pkubes@ucalgary.ca
See related article, pages 684–691
Key Words: Toll-like receptors • endothelial cells • atherosclerosis • hemodynamic shear
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Atherosclerosis is a chronic inflammatory disease modulated by both genetic and environmental factors.1–3 Disease onset is thought to be triggered by hypertension, high plasma concentrations of low-density lipoprotein (LDL) cholesterol, diabetes mellitus, or even infection.1 Endothelial injury by these factors is central to atherogenesis. Lesion susceptibility is greatest in those vascular regions with altered hemodynamics, such as the outer edges of arterial branches or curvatures. In these low-shear sites, endothelial proliferation, apoptosis, and permeability are all increased. In addition, the expression of adhesion molecules and chemokines increases, which facilitates the recruitment of monocytes, lymphocytes, and platelets from the circulation into the artery wall, resulting in the formation of an advanced, complicated lesion.2,3 With progressive subendothelial accumulation of cholesterol-engorged macrophages ("foam cells") and the accompanying formation of a fibrous cap encapsulating a necrotic core, atheromatous lesions can rupture, resulting in a thrombus that can cause myocardial infarction or stroke.1–3 Although what initiates and maintains this inflammatory state is unclear, it is intriguing that both myocardial infarction and stroke are increased during acute infections3 and numerous pathogens have been detected in human lesions. However, how pathogens contribute to atherosclerosis remains unclear.
The detection of microbial infection and the initiation of the innate immune response are mediated via germline-encoded, pattern-recognition receptors, including the Toll-like receptors (TLRs), which recognize highly conserved pathogen-associated molecular patterns.4–7 The ligation of many TLRs, including TLR2 (summarized in the Figure) and TLR4, results in the recruitment of the adaptor protein myeloid differentiation factor 88 (MyD88) followed by the
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