Open Access
Role of Toll-like receptor mediated signaling pathway in ischemic heart
Yasuchika Takeishi1,Isao Kubota1
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
DOI: 10.2741/3397 Volume 14 Issue 7, pp.2553-2558
Published: 01 January 2009

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.

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Yasuchika Takeishi, Isao Kubota. Role of Toll-like receptor mediated signaling pathway in ischemic heart. Frontiers in Bioscience-Landmark. 2009. 14(7); 2553-2558.