Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection

Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been ex...

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Autores principales:	Estefanía Tarazón, Carolina Gil-Cayuela, María García Manzanares, Marta Roca, Francisca Lago, José Ramón González-Juanatey, Elena Sánchez-Lacuesta, Luis Martínez-Dolz, Manuel Portolés, Esther Roselló-Lletí
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ea18da563d0148cd86d919cef693e595
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spelling	oai:doaj.org-article:ea18da563d0148cd86d919cef693e5952021-12-02T15:09:54ZCirculating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection10.1038/s41598-019-50413-82045-2322https://doaj.org/article/ea18da563d0148cd86d919cef693e5952019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50413-8https://doaj.org/toc/2045-2322Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p < 0.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC = 0.911, p < 0.0001), normal grafts vs. Grade 1 R (AUC = 0.819, p < 0.01), Grade 2 R (AUC = 0.911, p < 0.0001), Grade 3 R (AUC = 0.996, p < 0.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analysed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiology of rejection.Estefanía TarazónCarolina Gil-CayuelaMaría García ManzanaresMarta RocaFrancisca LagoJosé Ramón González-JuanateyElena Sánchez-LacuestaLuis Martínez-DolzManuel PortolésEsther Roselló-LletíNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Estefanía Tarazón Carolina Gil-Cayuela María García Manzanares Marta Roca Francisca Lago José Ramón González-Juanatey Elena Sánchez-Lacuesta Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
description	Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p < 0.0001). S1P discriminated between patients with and without rejection: normal grafts vs. all rejecting grafts (AUC = 0.911, p < 0.0001), normal grafts vs. Grade 1 R (AUC = 0.819, p < 0.01), Grade 2 R (AUC = 0.911, p < 0.0001), Grade 3 R (AUC = 0.996, p < 0.0001). In addition, we found changes in key enzymes and receptors of S1P pathway analysed on explanted hearts from heart failure patients. This preliminary study reveals that circulating S1P determination could be a novel approach to detect cardiac rejection, showing a robust capability for detection that improves gradually with the severity of rejection. These alterations could be relevant to better understand the involvement of calcium regulation on the pathophysiology of rejection.
format	article
author	Estefanía Tarazón Carolina Gil-Cayuela María García Manzanares Marta Roca Francisca Lago José Ramón González-Juanatey Elena Sánchez-Lacuesta Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí
author_facet	Estefanía Tarazón Carolina Gil-Cayuela María García Manzanares Marta Roca Francisca Lago José Ramón González-Juanatey Elena Sánchez-Lacuesta Luis Martínez-Dolz Manuel Portolés Esther Roselló-Lletí
author_sort	Estefanía Tarazón
title	Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
title_short	Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
title_full	Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
title_fullStr	Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
title_full_unstemmed	Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection
title_sort	circulating sphingosine-1-phosphate as a non-invasive biomarker of heart transplant rejection
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ea18da563d0148cd86d919cef693e595
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Circulating Sphingosine-1-Phosphate as A Non-Invasive Biomarker of Heart Transplant Rejection

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