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Coagulation, Protease-Activated Receptors, and Viral Myocarditis

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Abstract

The coagulation protease cascade plays an essential role in hemostasis. In addition, a clot contributes to host defense by limiting the spread of pathogens. Coagulation proteases induce intracellular signaling by cleavage of cell surface receptors called protease-activated receptors (PARs). These receptors allow cells to sense changes in the extracellular environment, such as infection. Viruses activate the coagulation cascade by inducing tissue factor expression and by disrupting the endothelium. Virus infection of the heart can cause myocarditis, cardiac remodeling, and heart failure. A recent study using a mouse model have shown that tissue factor, thrombin, and PAR-1 signaling all positively regulate the innate immune during viral myocarditis. In contrast, PAR-2 signaling was found to inhibit interferon-β expression and the innate immune response. These observations suggest that anticoagulants may impair the innate immune response to viral infection and that inhibition of PAR-2 may be a new strategy to reduce viral myocarditis.

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Acknowledgments

We thank Dr. Julie C. Williams for her careful and critical review of this manuscript. This work was supported by grants from the Myocarditis Foundation (to S. Antoniak) and the National Institutes of Health (to N. Mackman, HL119523).

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  1. Division of Hematology and Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, 98 Manning Drive, Campus Box 7035, Chapel Hill, NC, 27599, USA

    Silvio Antoniak & Nigel Mackman

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  1. Silvio Antoniak
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Correspondence to Silvio Antoniak.

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Associate Editor Daniel P. Judge oversaw the review of this article

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Antoniak, S., Mackman, N. Coagulation, Protease-Activated Receptors, and Viral Myocarditis. J. of Cardiovasc. Trans. Res. 7, 203–211 (2014). https://doi.org/10.1007/s12265-013-9515-7

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