title: Toll-like receptors: new players in myocardial ischemia/reperfusion injury.
abstract: Innate immune and inflammatory responses have been implicated in myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate immunity and inflammatory response are involved in myocardial I/R have not been elucidated completely. Recent studies highlight the role of Toll-like receptors (TLRs) in the induction of innate immune and inflammatory responses. Growing evidence has demonstrated that TLRs play a critical role in myocardial I/R injury. Specifically, deficiency of TLR4 protects the myocardium from ischemic injury, whereas modulation of TLR2 induces cardioprotection against ischemic insult. Importantly, cardioprotection induced by modulation of TLRs involves activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting that there is a crosstalk between TLRs and PI3K/Akt signaling pathways. In addition, TLRs also associate with other coreceptors, such as macrophage scavenger receptors in the recognition of their ligands. TLRs are also involved in the induction of angiogenesis, modulation of stem cell function, and expression of microRNA, which are currently important topic areas in myocardial I/R. Understanding how TLRs contribute to myocardial I/R injury could provide basic scientific knowledge for the development of new therapeutic approaches for the treatment and management of patients with heart attack.
authors.affiliation: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jim
authors.initials: J
authors.lastname: Kelley
authors.forename: Race
authors.initials: R
authors.lastname: Kao
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000942:Antigens, Bacterial; D050838:Interferon Regulatory Factor-3; D035683:MicroRNAs; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt