Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes

Abstract The endothelial glycocalyx (eGC) is considered a key regulator of several mechanisms that prevent vascular injury and disease. Degradation of this macromolecular layer may be associated with post-transplant graft dysfunction. In this study, we aimed to demonstrate the benefits of eGC protec...

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Autores principales:	Kentaro Noda, Brian J. Philips, Mark E. Snyder, Julie A. Phillippi, Mara Sullivan, Donna B. Stolz, Xi Ren, James D. Luketich, Pablo G. Sanchez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98cf30a0f9ce40b5b2955bce29674e74
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spelling	oai:doaj.org-article:98cf30a0f9ce40b5b2955bce29674e742021-12-02T17:52:25ZHeparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes10.1038/s41598-021-91777-02045-2322https://doaj.org/article/98cf30a0f9ce40b5b2955bce29674e742021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91777-0https://doaj.org/toc/2045-2322Abstract The endothelial glycocalyx (eGC) is considered a key regulator of several mechanisms that prevent vascular injury and disease. Degradation of this macromolecular layer may be associated with post-transplant graft dysfunction. In this study, we aimed to demonstrate the benefits of eGC protection via heparanase inhibition on graft quality. We established rat models of lung grafts with damaged or preserved eGC using ischemic insult and transplanted the grafts into recipients. Lung grafts were also subjected to normothermic ex vivo lung perfusion for detailed assessment under isolated conditions. Physiologic parameters and eGC-associated cellular events were assessed in grafts before and after reperfusion. Structurally degraded eGC and highly activated heparanase were confirmed in lungs with ischemic insult. After transplant, lungs with damaged eGC exhibited impaired graft function, inflammation, edema, and inflammatory cell migration. Increased eGC shedding was evident in the lungs after reperfusion both in vivo and ex vivo. These reperfusion-related deficiencies were significantly attenuated in lungs with preserved eGC following heparanase inhibition. Our studies demonstrated that eGC plays a key role in maintaining lung graft quality and function. Heparanase inhibition may serve as a potential therapeutic to preserve eGC integrity, leading to improved post-transplant outcomes.Kentaro NodaBrian J. PhilipsMark E. SnyderJulie A. PhillippiMara SullivanDonna B. StolzXi RenJames D. LuketichPablo G. SanchezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kentaro Noda Brian J. Philips Mark E. Snyder Julie A. Phillippi Mara Sullivan Donna B. Stolz Xi Ren James D. Luketich Pablo G. Sanchez Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
description	Abstract The endothelial glycocalyx (eGC) is considered a key regulator of several mechanisms that prevent vascular injury and disease. Degradation of this macromolecular layer may be associated with post-transplant graft dysfunction. In this study, we aimed to demonstrate the benefits of eGC protection via heparanase inhibition on graft quality. We established rat models of lung grafts with damaged or preserved eGC using ischemic insult and transplanted the grafts into recipients. Lung grafts were also subjected to normothermic ex vivo lung perfusion for detailed assessment under isolated conditions. Physiologic parameters and eGC-associated cellular events were assessed in grafts before and after reperfusion. Structurally degraded eGC and highly activated heparanase were confirmed in lungs with ischemic insult. After transplant, lungs with damaged eGC exhibited impaired graft function, inflammation, edema, and inflammatory cell migration. Increased eGC shedding was evident in the lungs after reperfusion both in vivo and ex vivo. These reperfusion-related deficiencies were significantly attenuated in lungs with preserved eGC following heparanase inhibition. Our studies demonstrated that eGC plays a key role in maintaining lung graft quality and function. Heparanase inhibition may serve as a potential therapeutic to preserve eGC integrity, leading to improved post-transplant outcomes.
format	article
author	Kentaro Noda Brian J. Philips Mark E. Snyder Julie A. Phillippi Mara Sullivan Donna B. Stolz Xi Ren James D. Luketich Pablo G. Sanchez
author_facet	Kentaro Noda Brian J. Philips Mark E. Snyder Julie A. Phillippi Mara Sullivan Donna B. Stolz Xi Ren James D. Luketich Pablo G. Sanchez
author_sort	Kentaro Noda
title	Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
title_short	Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
title_full	Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
title_fullStr	Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
title_full_unstemmed	Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
title_sort	heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/98cf30a0f9ce40b5b2955bce29674e74
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Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes

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