Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

Abstract It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-syst...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yankun Lyu, Vipin K. Verma, Younjee Lee, Iosif Taleb, Rachit Badolia, Thirupura S. Shankar, Christos P. Kyriakopoulos, Craig H. Selzman, William Caine, Rami Alharethi, Sutip Navankasattusas, Thomas Seidel, Stavros G. Drakos, Frank B. Sachse
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/59c6d15fd2db497ab916c8eb213cf9df
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:59c6d15fd2db497ab916c8eb213cf9df
record_format	dspace
spelling	oai:doaj.org-article:59c6d15fd2db497ab916c8eb213cf9df2021-12-02T16:53:17ZRemodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart10.1038/s41514-021-00066-72056-3973https://doaj.org/article/59c6d15fd2db497ab916c8eb213cf9df2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00066-7https://doaj.org/toc/2056-3973Abstract It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.Yankun LyuVipin K. VermaYounjee LeeIosif TalebRachit BadoliaThirupura S. ShankarChristos P. KyriakopoulosCraig H. SelzmanWilliam CaineRami AlharethiSutip NavankasattusasThomas SeidelStavros G. DrakosFrank B. SachseNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Yankun Lyu Vipin K. Verma Younjee Lee Iosif Taleb Rachit Badolia Thirupura S. Shankar Christos P. Kyriakopoulos Craig H. Selzman William Caine Rami Alharethi Sutip Navankasattusas Thomas Seidel Stavros G. Drakos Frank B. Sachse Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
description	Abstract It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.
format	article
author	Yankun Lyu Vipin K. Verma Younjee Lee Iosif Taleb Rachit Badolia Thirupura S. Shankar Christos P. Kyriakopoulos Craig H. Selzman William Caine Rami Alharethi Sutip Navankasattusas Thomas Seidel Stavros G. Drakos Frank B. Sachse
author_facet	Yankun Lyu Vipin K. Verma Younjee Lee Iosif Taleb Rachit Badolia Thirupura S. Shankar Christos P. Kyriakopoulos Craig H. Selzman William Caine Rami Alharethi Sutip Navankasattusas Thomas Seidel Stavros G. Drakos Frank B. Sachse
author_sort	Yankun Lyu
title	Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
title_short	Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
title_full	Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
title_fullStr	Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
title_full_unstemmed	Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
title_sort	remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/59c6d15fd2db497ab916c8eb213cf9df
work_keys_str_mv	AT yankunlyu remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT vipinkverma remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT younjeelee remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT iosiftaleb remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT rachitbadolia remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT thirupurasshankar remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT christospkyriakopoulos remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT craighselzman remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT williamcaine remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT ramialharethi remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT sutipnavankasattusas remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT thomasseidel remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT stavrosgdrakos remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart AT frankbsachse remodelingoftsystemandproteinsunderlyingexcitationcontractioncouplinginagingversusfailinghumanheart
_version_	1718382859557797888

Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

Ejemplares similares