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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doaj-36d2e0e86de94933905fe03e513027e22020-11-25T02:06:08ZengPublic 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 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junxi Wu Patrick W F Hadoke Kaloyan Takov Agnieszka Korczak Martin A Denvir Lee B Smith |
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 |
author_facet |
Junxi Wu Patrick W F Hadoke Kaloyan Takov Agnieszka Korczak Martin A Denvir Lee B Smith |
author_sort |
Junxi Wu |
title |
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_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_sort |
influence of androgen receptor in vascular cells on reperfusion following hindlimb ischaemia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
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. |
url |
http://europepmc.org/articles/PMC4861284?pdf=render |
work_keys_str_mv |
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1724934841813696512 |