Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.

AIMS:Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlim...

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Main Authors: Junxi Wu, Patrick W F Hadoke, Kaloyan Takov, Agnieszka Korczak, Martin A Denvir, Lee B Smith
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4861284?pdf=render
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author Junxi Wu
Patrick W F Hadoke
Kaloyan Takov
Agnieszka Korczak
Martin A Denvir
Lee B Smith
author_facet Junxi Wu
Patrick W F Hadoke
Kaloyan Takov
Agnieszka Korczak
Martin A Denvir
Lee B Smith
author_sort Junxi Wu
collection DOAJ
description AIMS:Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall. METHODS AND RESULTS:Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10(-10)-10(-7)M; 6 days). CONCLUSION:These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.
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spelling doaj.art-36d2e0e86de94933905fe03e513027e22022-12-21T19:29:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015498710.1371/journal.pone.0154987Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.Junxi WuPatrick W F HadokeKaloyan TakovAgnieszka KorczakMartin A DenvirLee B SmithAIMS:Studies in global androgen receptor knockout (G-ARKO) and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall. METHODS AND RESULTS:Mice with selective deletion of AR (ARKO) from vascular smooth muscle cells (SM-ARKO), endothelial cells (VE-ARKO), or both (SM/VE-ARKO) were compared with wild type (WT) controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO) did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture) model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10(-10)-10(-7)M; 6 days). CONCLUSION:These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.http://europepmc.org/articles/PMC4861284?pdf=render
spellingShingle Junxi Wu
Patrick W F Hadoke
Kaloyan Takov
Agnieszka Korczak
Martin A Denvir
Lee B Smith
Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
PLoS ONE
title Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
title_full Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
title_fullStr Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
title_full_unstemmed Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
title_short Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.
title_sort influence of androgen receptor in vascular cells on reperfusion following hindlimb ischaemia
url http://europepmc.org/articles/PMC4861284?pdf=render
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AT agnieszkakorczak influenceofandrogenreceptorinvascularcellsonreperfusionfollowinghindlimbischaemia
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