Inflammation and Heart Diseases: Role of Toll-Like Receptor Signaling

Wei Chao
Department of Anesthesia, Critical Care and PainMedicine,Massachusetts General Hospital, Harvard Medical School, Boston,USA
J Anesth Perioper Med 2014; 1(2): 104- 117 . Published on Nov 25, 2014 . doi:10.24015/JAPM.2014.0016
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Aim of review: Heart diseases such as septic cardiomyopathy, ischemic myocardial injury and acute myocarditis pose significant perioperative risk to surgical patients and present challenges to anesthesiologists. Myocardial inflammation is a common theme of these diseases and plays an important role in their pathogeneses. Toll-like receptors (TLRs) are an important part of the innate immune system. The aim of this article is to provide a brief review on the major landmark studies of TLRs and their signaling, the complex and critical role of TLRs in severe sepsis, ischemic myocardial injury, and myocarditis. The article intends to cover animal studies defining the molecular mechanisms by which TLR signaling contributes to the pathogenesis of these heart diseases as well as the recent clinical trials targeting TLR for sepsis intervention.

Method: Literatures were searched via PubMed with the key words TLRs, sepsis, myocardial ischemia, and myocarditis. A few previously published review articles in the relevant fields were referenced.

Recent findings: TLRs detect invading pathogens through the pathogen-associated molecular pattern (PAMP) recognition and play an essential role in the host defense. TLRs can also sense endogenous molecules with the danger-associated molecular pattern (DAMP), such as heat shock proteins (HSPs), high mobility group 1 (HMGB-1) and extracellular RNA, which are produced under various injurious conditions. Studies in the past decade have clearly established the critical role of TLR signaling in mediating cardiac inflammation in the context of severe sepsis, myocardial ischemia-reperfusion injury and acute myocarditis. A variety of microbial and non-microbial TLR ligands have been identified under these critical conditions. These ligands act through TLRs and elicit potent biochemical and inflammatory responses. By mediating the complex cardiac as well as systemic inflammation, either beneficial or deleterious in nature, TLRs play a pivotal role in the development of these cardiac diseases. Recent TLR4 antagonist (eritoran) Phase I-III clinical trials represent the latest effort targeting TLR signaling for sepsis therapeutics.

Summary: Studies of the past decade have firmly established the role of TLR signaling in cardiac inflammation and dysfunction during severe sepsis, ischemic myocardial injury, and acute myocarditis. Understanding the complex cellular and molecular pathways by which TLR signaling controls myocardial inflammation and injury provides insight into the mechanisms of these cardiac diseases and will impact on how we diagnose and treat these critical conditions in the future.



Citation: Wei Chao. Inflammation and heart diseases: role of toll-like receptor signaling. J Anesth Perioper Med 2014; 1: 104-17. doi: 10.24015/JAPM.2014.0016

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