The Glomerular Endothelium Restricts Albumin Filtration

Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Anothe...

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Autores principales:	Barbara J. Ballermann, Jenny Nyström, Börje Haraldsson
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	endothelial surface layer endothelial dysfunction fenestrae glycocalyx hyaluronan permselectivity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8ff98907a0ea43b6b49f2e4fe4d116c4
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id	oai:doaj.org-article:8ff98907a0ea43b6b49f2e4fe4d116c4
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spelling	oai:doaj.org-article:8ff98907a0ea43b6b49f2e4fe4d116c42021-12-01T13:19:53ZThe Glomerular Endothelium Restricts Albumin Filtration2296-858X10.3389/fmed.2021.766689https://doaj.org/article/8ff98907a0ea43b6b49f2e4fe4d116c42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.766689/fullhttps://doaj.org/toc/2296-858XInflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.Barbara J. BallermannJenny NyströmBörje HaraldssonFrontiers Media S.A.articleendothelial surface layerendothelial dysfunctionfenestraeglycocalyxhyaluronanpermselectivityMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endothelial surface layer endothelial dysfunction fenestrae glycocalyx hyaluronan permselectivity Medicine (General) R5-920
spellingShingle	endothelial surface layer endothelial dysfunction fenestrae glycocalyx hyaluronan permselectivity Medicine (General) R5-920 Barbara J. Ballermann Jenny Nyström Börje Haraldsson The Glomerular Endothelium Restricts Albumin Filtration
description	Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.
format	article
author	Barbara J. Ballermann Jenny Nyström Börje Haraldsson
author_facet	Barbara J. Ballermann Jenny Nyström Börje Haraldsson
author_sort	Barbara J. Ballermann
title	The Glomerular Endothelium Restricts Albumin Filtration
title_short	The Glomerular Endothelium Restricts Albumin Filtration
title_full	The Glomerular Endothelium Restricts Albumin Filtration
title_fullStr	The Glomerular Endothelium Restricts Albumin Filtration
title_full_unstemmed	The Glomerular Endothelium Restricts Albumin Filtration
title_sort	glomerular endothelium restricts albumin filtration
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8ff98907a0ea43b6b49f2e4fe4d116c4
work_keys_str_mv	AT barbarajballermann theglomerularendotheliumrestrictsalbuminfiltration AT jennynystrom theglomerularendotheliumrestrictsalbuminfiltration AT borjeharaldsson theglomerularendotheliumrestrictsalbuminfiltration AT barbarajballermann glomerularendotheliumrestrictsalbuminfiltration AT jennynystrom glomerularendotheliumrestrictsalbuminfiltration AT borjeharaldsson glomerularendotheliumrestrictsalbuminfiltration
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The Glomerular Endothelium Restricts Albumin Filtration

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