Chantelle M Rein-Smith1, Frank C Church. 1. 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.
Abstract
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.
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.
Authors: Carles Vilariño-Güell; Alexander Zimprich; Filippo Martinelli-Boneschi; Bruno Herculano; Zhe Wang; Fuencisla Matesanz; Elena Urcelay; Koen Vandenbroeck; Laura Leyva; Denis Gris; Charbel Massaad; Jacqueline A Quandt; Anthony L Traboulsee; Mary Encarnacion; Cecily Q Bernales; Jordan Follett; Irene M Yee; Maria G Criscuoli; Angela Deutschländer; Eva M Reinthaler; Tobias Zrzavy; Elisabetta Mascia; Andrea Zauli; Federica Esposito; Antonio Alcina; Guillermo Izquierdo; Laura Espino-Paisán; Jorge Mena; Alfredo Antigüedad; Patricia Urbaneja-Romero; Jesús Ortega-Pinazo; Weihong Song; A Dessa Sadovnick Journal: PLoS Genet Date: 2019-06-06 Impact factor: 5.917