Toll-like receptors: new players in myocardial ischemia/reperfusion injury

• Published in: Antioxidants & redox signaling Vol. 15; no. 7; p. 1875
• Main Authors: Ha, Tuanzhu, Liu, Li, Kelley, Jim, Kao, Race, Williams, David, Li, Chuanfu
• Format: Journal Article
• Language: English
• Published: United States 01-10-2011
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Animals; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Gene Silencing; Genetic Therapy; Humans; Immunity, Innate - genetics; Inflammation; Interferon Regulatory Factor-3 - metabolism; MicroRNAs - genetics; Myeloid Differentiation Factor 88 - metabolism; Myocardial Ischemia - genetics; Myocardial Ischemia - immunology; Myocardial Ischemia - metabolism; Myocardial Ischemia - therapy; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - immunology; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - therapy; NF-kappa B - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Protein Transport; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Signal Transduction; Stem Cell Transplantation; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism
• ISSN: 1557-7716
• DOI: 10.1089/ars.2010.3723

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.