Journal article
Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II-Induced Aortic Aneurysm and Atherosclerosis
SM Krishna, SW Seto, RJ Jose, J Li, SK Morton, E Biros, Y Wang, V Nsengiyumva, JHN Lindeman, GG Loots, CM Rush, JM Craig, J Golledge
Arteriosclerosis Thrombosis and Vascular Biology | LIPPINCOTT WILLIAMS & WILKINS | Published : 2017
Abstract
Objective-Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. Approach and Results-SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE-/-) mice (SOSTTg.ApoE-/-) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were signif..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work is funded in part by grants from the National Health and Medical Research Council (1079369, 1079193, 1063476, 1021416, and 1000967), the Queensland Government, the Townsville Hospital Private Practice Trust, the Research Infrastructure Block Grant, and the Medicine Incentive Grant, School of Medicine, James Cook University. J. Golledge holds a Practitioner Fellowship from the National Health and Medical Research Council, Australia (1019921), and a Senior Clinical Research Fellowship from the Queensland Government. S.-W. Seto is a past recipient of fellowships from the NHMRC, Australia (1016349), and the Australian National Heart Foundation (PD12B6825). The funding bodies played no role in generation of the data presented in this publication.