Plasminflammation-An Emerging Pathway to Bradykinin Production.

Abstract:

:Plasminogen activation is essential for fibrinolysis-the breakdown of fibrin polymers in blood clots. Besides this important function, plasminogen activation participates in a wide variety of inflammatory conditions. One of these conditions is hereditary angioedema (HAE), a rare disease with characteristic attacks of aggressive tissue swelling due to unregulated production and activity of the inflammatory mediator bradykinin. Plasmin was already implicated in this disease decades ago, but a series of recent discoveries have made it clear that plasmin actively contributes to this pathology. Collective evidence points toward an axis in which the plasminogen activation system and the contact system (which produces bradykinin) are mechanistically coupled. This is amongst others supported by findings in subtypes of HAE that are caused by gain-of-function mutations in the genes that respectively encode factor XII or plasminogen, as well as clinical experience with the antifibrinolytic agents in HAE. The concept of a link between plasminogen activation and the contact system helps us to explain the inflammatory side effects of fibrinolytic therapy, presenting as angioedema or tissue edema. Furthermore, these observations motivate the development and characterization of therapeutic agents that disconnect plasminogen activation from bradykinin production.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Maas C

doi

10.3389/fimmu.2019.02046

subject

Has Abstract

pub_date

2019-08-27 00:00:00

pages

2046

issn

1664-3224

journal_volume

10

pub_type

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