期刊
BLOOD
卷 133, 期 6, 页码 511-520出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2018-07-818211
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资金
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01DK105099]
- National Institutes of Health, National Institute of Environmental Health Sciences [R01ES017537]
- National Institutes of Health, National Cancer Institute [R01CA211098]
- National Institutes of Health, National Heart, Lung, and Blood Institute [U01HL143403]
- Department of Orthopaedics and Rehabilitation-Vanderbilt University Medical Center
- Caitlin Lovejoy Fund
The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological end points of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro) thrombin and plasmin(ogen), have powerful roles in driving acute and reparative inflammatory pathways that affect the spectrum of tissue injury, remodeling, and repair. Indeed, fibrin(ogen) deposits are a near-universal feature of tissue injury, regardless of the nature of the inciting event, including injuries driven by mechanical insult, infection, or immunological derangements. Fibrin can modify multiple aspects of inflammatory cell function by engaging leukocytes through a variety of cellular receptors and mechanisms. Studies on the role of coagulation system activation and fibrin(ogen) deposition in models of inflammatory disease and tissue injury have revealed points of commonality, as well as context-dependent contributions of coagulation and fibrinolytic factors. However, there remains a critical need to define the precise temporal and spatial mechanisms by which fibrinogen-directed inflammatory events may dictate the severity of tissue injury and coordinate the remodeling and repair events essential to restore normal organ function. Current research trends suggest that future studies will give way to the identification of novel hemostatic factor-targeted therapies for a range of tissue injuries and disease.
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