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Fibrinogen as a key regulator of inflammation in disease

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Abstract

The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer’s disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

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Acknowledgments

We thank Gary Howard for editorial assistance. This work was supported by the National Multiple Sclerosis Society grant RG4595A1/T to D.D. and the National Institutes of Health/National Institute of Neurological Disorders and Stroke R01 grants NS051470, NS052189, and NS066361 to K.A.

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The authors declare that they have no competing financial or other interests related to this manuscript.

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  1. Gladstone Institute of Neurological Disease, University of California, San Francisco, 1650 Owens St, San Francisco, CA, 94158, USA

    Dimitrios Davalos & Katerina Akassoglou

  2. Department of Neurology, University of California, San Francisco, San Francisco, CA, USA

    Katerina Akassoglou

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  1. Dimitrios Davalos
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Correspondence to Katerina Akassoglou.

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This article is published as part of the Special Issue on Coagulation & Inflammation [34:1]

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Davalos, D., Akassoglou, K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34, 43–62 (2012). https://doi.org/10.1007/s00281-011-0290-8

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