Therapeutic targeting of innate immunity in the failing heart

Veli K. Topkara, Sarah Evans, Weili Zhang, Slava Epelman, Lora Staloch, Philip M. Barger, Douglas L. Mann

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

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".

Original languageEnglish
Pages (from-to)594-599
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number4
DOIs
StatePublished - Oct 1 2011

Keywords

  • Cardiac remodeling
  • Damage-associated molecular
  • Innate immunity
  • Patterns
  • Toll-like receptors

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