Journal article

Kallikrein-1 Blockade Inhibits Aortic Expansion in a Mouse Model and Reduces Prostaglandin E2 Secretion From Human Aortic Aneurysm Explants

Corey S Moran, Erik Biros, Smriti M Krishna, Susan K Morton, Daniel J Sexton, Jonathan Golledge

JOURNAL OF THE AMERICAN HEART ASSOCIATION | WILEY | Published : 2021

Abstract

Background Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high- and low-molecular-weight kininogen by the serine protease kallikrein-1. The aims of this study were first to examine the effect of neutralizing kallikrein-1 on AAA development in a mouse model and second to test how blocking kallikrein-1 affected cyclooxygenase-2 and prostaglandin E2 in human AAA explants. Methods and Results Neutralization of kallikrein-1 in apolipoprotein E-deficient (ApoE-/-) mice via administration of a blocking antibody inhibited..

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Grants

Awarded by National Health and Medical Research Council


Awarded by National Health and Medical Research Council, Australia


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (1098717, 1079369) and Queensland Government. Golledge holds a Practitioner Fellowship from the National Health and Medical Research Council, Australia (1117061) and a Senior Clinical Research Fellowship from the Queensland Government, Australia. The funding bodies played no role in the production of this publication.