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Emerging pathophysiological roles for fibrinolysis

Rein-Smith, Chantelle M.a; Church, Frank C.a,b

doi: 10.1097/MOH.0000000000000068
HEMOSTASIS AND THROMBOSIS: Edited by Joseph E. Italiano and Jorge A. Di Paola

Purpose of review The fibrinolytic system plays a key role in the regulation of hemostasis and thrombosis; however, it also has multiple pleiotropic effects. In this review, we examine the studies that investigated the role of the plasminogen activator system and its inhibitors outside the context of clot lysis.

Recent findings Activators of plasminogen, plasminogen receptors, and inhibitors of plasminogen activation all play a role in the proliferation, migration, and metastasis of tumor cells in many cancer types and may serve as prognostic and diagnostic markers. The plasminogen activator system is also involved in the pathogenesis and severity of several inflammatory diseases, including sepsis, metabolic disease, arthritis, and airway disease. A study on the use of tissue plasminogen activator (tPA) following cerebrovascular events demonstrates that tPA also plays important roles in the pathogenesis of stroke and affects the long-term outcomes.

Summary Current evidence suggests an association between the plasminogen activator system and its inhibitors in a variety of malignant and inflammatory states. Newly discovered roles for plasminogen activators and plasminogen activator inhibitors in these diseases provide novel targets for future therapeutic development. Additionally, the newly characterized regulation of the plasminogen activator system by endogenous microRNAs provides new insight into the physiological role of this system and its role in disease.

aMcAllister Heart Institute

bDepartment of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Correspondence to Frank C. Church, PhD, Division of Hematology and Oncology/Medicine, University of North Carolina School of Medicine, 302 Mary Ellen Jones Building, Chapel Hill, NC 27599-7035, USA. Tel: +1 919 966 3313; fax: +1 919 966 7639; e-mail:

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