Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron

Abstract Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF...

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Autores principales:	Nabil A. Rashdan, Bo Zhai, Pamela C. Lovern
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b2bda72861c4b6da865a02ca390da62
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spelling	oai:doaj.org-article:8b2bda72861c4b6da865a02ca390da622021-12-02T17:55:13ZFluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron10.1038/s41598-021-94559-w2045-2322https://doaj.org/article/8b2bda72861c4b6da865a02ca390da622021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94559-whttps://doaj.org/toc/2045-2322Abstract Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.Nabil A. RashdanBo ZhaiPamela C. LovernNature 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 Nabil A. Rashdan Bo Zhai Pamela C. Lovern Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
description	Abstract Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.
format	article
author	Nabil A. Rashdan Bo Zhai Pamela C. Lovern
author_facet	Nabil A. Rashdan Bo Zhai Pamela C. Lovern
author_sort	Nabil A. Rashdan
title	Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
title_short	Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
title_full	Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
title_fullStr	Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
title_full_unstemmed	Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
title_sort	fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8b2bda72861c4b6da865a02ca390da62
work_keys_str_mv	AT nabilarashdan fluidshearstressregulatesplacentalgrowthfactorexpressionviahemeoxygenase1andiron AT bozhai fluidshearstressregulatesplacentalgrowthfactorexpressionviahemeoxygenase1andiron AT pamelaclovern fluidshearstressregulatesplacentalgrowthfactorexpressionviahemeoxygenase1andiron
_version_	1718379120948150272

Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron

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