Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy

Abstract Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM...

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Autores principales: Kristina Sonnenschein, Jan Fiedler, David de Gonzalo-Calvo, Ke Xiao, Angelika Pfanne, Annette Just, Carolin Zwadlo, Samira Soltani, Udo Bavendiek, Theresia Kraft, Cristobal Dos Remedios, Serghei Cebotari, Johann Bauersachs, Thomas Thum
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/512e2ec0033c4485af4d7813594d8685
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spelling oai:doaj.org-article:512e2ec0033c4485af4d7813594d86852021-12-02T13:51:06ZBlood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy10.1038/s41598-020-80868-z2045-2322https://doaj.org/article/512e2ec0033c4485af4d7813594d86852021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80868-zhttps://doaj.org/toc/2045-2322Abstract Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.Kristina SonnenscheinJan FiedlerDavid de Gonzalo-CalvoKe XiaoAngelika PfanneAnnette JustCarolin ZwadloSamira SoltaniUdo BavendiekTheresia KraftCristobal Dos RemediosSerghei CebotariJohann BauersachsThomas ThumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kristina Sonnenschein
Jan Fiedler
David de Gonzalo-Calvo
Ke Xiao
Angelika Pfanne
Annette Just
Carolin Zwadlo
Samira Soltani
Udo Bavendiek
Theresia Kraft
Cristobal Dos Remedios
Serghei Cebotari
Johann Bauersachs
Thomas Thum
Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
description Abstract Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.
format article
author Kristina Sonnenschein
Jan Fiedler
David de Gonzalo-Calvo
Ke Xiao
Angelika Pfanne
Annette Just
Carolin Zwadlo
Samira Soltani
Udo Bavendiek
Theresia Kraft
Cristobal Dos Remedios
Serghei Cebotari
Johann Bauersachs
Thomas Thum
author_facet Kristina Sonnenschein
Jan Fiedler
David de Gonzalo-Calvo
Ke Xiao
Angelika Pfanne
Annette Just
Carolin Zwadlo
Samira Soltani
Udo Bavendiek
Theresia Kraft
Cristobal Dos Remedios
Serghei Cebotari
Johann Bauersachs
Thomas Thum
author_sort Kristina Sonnenschein
title Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
title_short Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
title_full Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
title_fullStr Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
title_full_unstemmed Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
title_sort blood-based protein profiling identifies serum protein c-kit as a novel biomarker for hypertrophic cardiomyopathy
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/512e2ec0033c4485af4d7813594d8685
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