Abstract
Despite advances in treatment of patients who suffer from ischemic heart disease, morbidity related to myocardial infarction is increasing in Western societies. Acute and chronic immune responses elicited by myocardial ischemia have an important role in the functional deterioration of the heart. Research on modulation of the inflammatory responses was focused on effector mediators such as leukocytes. However, increasing evidence indicates that various endogenous ligands that act as 'danger signals', also called danger-associated molecular patterns (DAMPs), are released upon injury and modulate inflammation. Originally described as part of the first-line defense against invading microorganisms, several Toll-like receptors (TLRs) on leukocytes and parenchymal cells have now been shown to respond to such signals and to have a pivotal role in noninfectious pathological cardiovascular conditions, such as ischemia–reperfusion injury and heart failure. From a therapeutic perspective, DAMPs are attractive targets owing to their specific induction after injury. In this Review, we will discuss innate immune activation through TLRs in cardiac ischemia mediated by DAMPs.
Key Points
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Innate immune responses are critical mediators of tissue damage and repair after myocardial infarction
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Cells involved in innate immunity also recognize and become activated by molecules released after cell death or by matrix degradation products, so-called 'danger signals' or danger-associated molecular patterns (DAMPs)
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Toll-like receptors on cardiac and circulating cells recognize pathogen-associated molecular patterns as well as DAMPs and are important mediators of inflammatory reactions after cardiac ischemia
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Preclinical studies show that DAMPs are promising targets to enhance myocardial viability and repair after myocardial infarction
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As several DAMPs are necessary for proper wound healing, therapeutic interference with DAMP-related signaling in patients after myocardial infarction necessitates careful evaluation and further research
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Acknowledgements
The authors would like to thank Professor N. G. Frangogiannis for his critical review of the manuscript. This work is supported by research grants from The Netherlands Organization for Scientific Research and Utrecht University Mozaïek grant (contract 017.004.004 to F. Arslan) and Netherlands Heart Foundation (contract 2010T001 to F. Arslan).
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F. Arslan researched data and wrote the manuscript. G. Pasterkamp and D. P. de Kleijn reviewed and edited the article before submission.
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Arslan, F., de Kleijn, D. & Pasterkamp, G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol 8, 292–300 (2011). https://doi.org/10.1038/nrcardio.2011.38
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