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01 April 2011

Toll-like receptor and its roles in myocardial ischemic/reperfusion injury

Yu Fang, Jianguo Hu

DOI: 10.12659/MSM.881709

Med Sci Monit 2011; 17(4): RA100-109

Abstract

ABSTRACT: The innate immune system, mediated via toll-like receptors (TLRs), represents the first line of defensive mechanisms that protects hosts from invading microbial pathogens. TLRs are a family of pattern recognition receptors (PRRs), and are pathologically activated by a set of pathogen-associated microbial patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLRs deliver signals via a specific intracellular signaling pathway involving distinctive adaptor proteins and protein kinases, and ultimately initiate transcriptional factors resulting in inflammatory responses. TLR4 is a paramount type of TLRs, located in the heart, and plays an important role in mediating myocardial ischemic reperfusion (I/R) injury. Loss-of-function experiments and animal models using genetic techniques have found that the MyD88-independent and the MyD88-dependent pathways together participate in the pathological process of myocardial I/R injury. Some other distinctive signaling pathways, such as the PI3K/AKt and AMPK/ERK pathways, interacting with the TLR4 signaling pathway, were also found to be causes of myocardial I/R injury. These different pathways activate a series of downstream transcriptional factors, produced a great quantity of inflammatory cytokines, such as IL, TNF, and initiate inflammatory response. This results in cardiac injury and dysfunction, such as myocardial stunning, no reflow phenomenon, reperfusion arrhythmias and lethal reperfusion injury, and other related complication such as ventricular remodeling. In the future, blockades aimed at blocking the signaling pathway could benefit developments in pharmacology.

Keywords: Myocardial Reperfusion Injury - physiopathology, Inflammation - pathology, Heart Function Tests, Cytokines - metabolism, Signal Transduction, Toll-Like Receptors - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750