Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion

Abstract We previously identified the inhibitory serpin protease nexin-1 (PN-1) as an important player of the angiogenic balance with anti-angiogenic activity in physiological conditions. In the present study, we aimed to determine the role of PN-1 on pathological angiogenesis and particularly in re...

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Autores principales:	Sonia Selbonne, Celina Madjene, Benjamin Salmon, Yacine Boulaftali, Marie-Christine Bouton, Véronique Arocas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e13bbebf55f44816aa7f01fcf805e533
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spelling	oai:doaj.org-article:e13bbebf55f44816aa7f01fcf805e5332021-12-02T16:10:35ZProtease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion10.1038/s41598-021-92794-92045-2322https://doaj.org/article/e13bbebf55f44816aa7f01fcf805e5332021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92794-9https://doaj.org/toc/2045-2322Abstract We previously identified the inhibitory serpin protease nexin-1 (PN-1) as an important player of the angiogenic balance with anti-angiogenic activity in physiological conditions. In the present study, we aimed to determine the role of PN-1 on pathological angiogenesis and particularly in response to ischemia, in the mouse model induced by femoral artery ligation. In wild-type (WT) muscle, we observed an upregulation of PN-1 mRNA and protein after ischemia. Angiography analysis showed that femoral artery perfusion was more rapidly restored in PN-1−/− mice than in WT mice. Moreover, immunohistochemistry showed that capillary density increased following ischemia to a greater extent in PN-1−/− than in WT muscles. Moreover, leukocyte recruitment and IL-6 and MCP-1 levels were also increased in PN-1−/− mice compared to WT after ischemia. This increase was accompanied by a higher overexpression of the growth factor midkine, known to promote leukocyte trafficking and to modulate expression of proinflammatory cytokines. Our results thus suggest that the higher expression of midkine observed in PN-1- deficient mice can increase leukocyte recruitment in response to higher levels of MCP-1, finally driving neoangiogenesis. Thus, PN-1 can limit neovascularisation in pathological conditions, including post-ischemic reperfusion of the lower limbs.Sonia SelbonneCelina MadjeneBenjamin SalmonYacine BoulaftaliMarie-Christine BoutonVéronique ArocasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonia Selbonne Celina Madjene Benjamin Salmon Yacine Boulaftali Marie-Christine Bouton Véronique Arocas Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
description	Abstract We previously identified the inhibitory serpin protease nexin-1 (PN-1) as an important player of the angiogenic balance with anti-angiogenic activity in physiological conditions. In the present study, we aimed to determine the role of PN-1 on pathological angiogenesis and particularly in response to ischemia, in the mouse model induced by femoral artery ligation. In wild-type (WT) muscle, we observed an upregulation of PN-1 mRNA and protein after ischemia. Angiography analysis showed that femoral artery perfusion was more rapidly restored in PN-1−/− mice than in WT mice. Moreover, immunohistochemistry showed that capillary density increased following ischemia to a greater extent in PN-1−/− than in WT muscles. Moreover, leukocyte recruitment and IL-6 and MCP-1 levels were also increased in PN-1−/− mice compared to WT after ischemia. This increase was accompanied by a higher overexpression of the growth factor midkine, known to promote leukocyte trafficking and to modulate expression of proinflammatory cytokines. Our results thus suggest that the higher expression of midkine observed in PN-1- deficient mice can increase leukocyte recruitment in response to higher levels of MCP-1, finally driving neoangiogenesis. Thus, PN-1 can limit neovascularisation in pathological conditions, including post-ischemic reperfusion of the lower limbs.
format	article
author	Sonia Selbonne Celina Madjene Benjamin Salmon Yacine Boulaftali Marie-Christine Bouton Véronique Arocas
author_facet	Sonia Selbonne Celina Madjene Benjamin Salmon Yacine Boulaftali Marie-Christine Bouton Véronique Arocas
author_sort	Sonia Selbonne
title	Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
title_short	Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
title_full	Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
title_fullStr	Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
title_full_unstemmed	Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
title_sort	protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e13bbebf55f44816aa7f01fcf805e533
work_keys_str_mv	AT soniaselbonne proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion AT celinamadjene proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion AT benjaminsalmon proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion AT yacineboulaftali proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion AT mariechristinebouton proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion AT veroniquearocas proteasenexin1deficiencyincreasesmousehindlimbneovascularisationfollowingischemiaandacceleratesfemoralarteryperfusion
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Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion

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