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

Abstract

SummaryThe 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.

Resveratrol inhibitsStaphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells

“…Numerous studies have implicated PI3K as a regulator of TLR signalling [30], and we have shown in the present study that inhibition of PI3K and Akt reduced heat-killed S. aureus-induced VCAM-1 expression. We also established that heat-killed S. aureus caused the formation of a TLR2-MyD88-PI3K complex and then induced Akt activation.…”

Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats

“…Ischemic heart disease is the primary cause of mortality and morbidity all over the world (2). Rapid reperfusion is critical in the treatment of myocardial ischemic incidents, and blood flow restoration is necessary for the salvage of endangered myocardium after MI (3,4).…”

Implication of Pattern-Recognition Receptors in Cardiovascular Diseases

“…Another group consists of TLR3, 7, 8 and 9, which are present exclusively in intracellular vesicles, and recognize nucleic acids derived from viruses and bacteria (51). Recently discovered mouse TLR11, 12 and 13 are believed to be plasma membrane localized (30). In addition to exogenous pathogen-derived ligands, many endogenous TLR ligands such as high-mobility group box1 (HMGB1), fibrinogen, and heat shock proteins are identified (Figure 2).…”