title: Therapeutic targeting of innate immunity in the failing heart.
abstract: Recent studies suggest that the heart possesses an intrinsic system that is intended to delimit tissue injury, as well as orchestrate homoeostatic responses within the heart. The extant literature suggests that this intrinsic stress response is mediated, at least in part, by a family of pattern recognition receptors that belong to the innate immune system, including CD14, the soluble pattern recognition receptor for lipopolysaccharide, and Toll-like receptors 2, 3, 4, 5, 6, 7, and 9. Although this intrinsic stress response system provides a short-term adaptive response to tissue injury, the beneficial effects of this phylogenetically ancient system may be lost if myocardial expression of these molecules either becomes sustained and/or excessive, in which case the salutary effects of activation of these pathways are contravened by the known deleterious effects of inflammatory signaling. Herein we present new information with regard to activation of innate immune gene expression in the failing human heart, as well as review the novel TLR antagonists that are being developed for other indications outside of heart failure. This review will discuss the interesting possibility that the TLR pathway may represent a new target for the development of novel heart failure therapeutics. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."
authors.affiliation: Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8086, St. Louis, MO 63110, USA.
authors.forename: Veli K
authors.initials: VK
authors.lastname: Topkara
authors.forename: Sarah
authors.initials: S
authors.lastname: Evans
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.forename: Slava
authors.initials: S
authors.lastname: Epelman
authors.forename: Lora
authors.initials: L
authors.lastname: Staloch
authors.forename: Philip M
authors.initials: PM
authors.lastname: Barger
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000818:Animals; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D057170:Translational Research, Biomedical; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D051193:Toll-Like Receptors