Role of Toll-like receptor mediated signaling pathway in ischemic heart

Front Biosci (Landmark Ed). 2009 Jan 1;14:2553-8. doi: 10.2741/3397.

Abstract

Stimulation of TLRs by exogenous and endogenous ligands triggers expression of several genes that are involved in innate immune responses. Recently, a role of TLR4 in the myocardial response to injury separate from microbial pathogens has been examined in experimental studies. TLR4 deficient mice sustain significantly smaller infarctions compared with wild-type control mice given similar areas at risk. Levels of serum cytokines such as IL-1b, IL-6, and TNFa are increased after ischemia/reperfusion, but these responses are attenuated in TLR4 deficient mice compared to control mice. TLR2 signaling also importantly contributes to cardiac dysfunction following ischemia/reperfusion. MyD88, a key adaptor protein for TLR signaling, is responsible for the protective effects of TLR signaling inhibition in ischemia/reperfusion injury. TLR4 gene polymorphism (Asp299Gly) attenuates innate immune responsiveness, reduces the risk for coronary artery disease, and increases a chance of longevity. The innate immune system is clearly involved in the pathogenesis of cardiovascular diseases and could be a new therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Myeloid Differentiation Factor 88 / metabolism
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology*
  • Myocardium / metabolism
  • Polymorphism, Genetic
  • Signal Transduction / physiology*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Toll-Like Receptors / physiology*

Substances

  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptors