Role of plasma kallikrein in diabetes and metabolism

Edward P. Feener; Qunfang Zhou; Ward Fickweiler

doi:10.1160/TH13-02-0179

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(03): 434-441
DOI: 10.1160/TH13-02-0179

Theme Issue Article

Schattauer GmbH

Role of plasma kallikrein in diabetes and metabolism

Edward P. Feener

¹Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachussetts, USA

,

Qunfang Zhou

¹Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachussetts, USA

,

Ward Fickweiler

¹Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachussetts, USA

› Author Affiliations

Abstract

Summary

Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.

Keywords

Plasma kallikrein - diabetes - Klkb1 - contact activation pathway

Full Text

References

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