Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy

Abstract Dilated cardiomyopathy (DCM), as characterized by the left ventricular dilatation and contractile dysfunction, is one of the molecular mechanisms of which are largely unexplored. Here, we profiled the region‐resolved transcriptome and proteome of healthy and DCM human myocardial tissue and...

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Main Authors: Ling Lin, Shanshan Liu, Zhangwei Chen, Yan Xia, Juanjuan Xie, Mingqiang Fu, Danbo Lu, Yuan Wu, Huali Shen, Pengyuan Yang, Juying Qian
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:View
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Online Access:https://doi.org/10.1002/VIW.20220040
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author Ling Lin
Shanshan Liu
Zhangwei Chen
Yan Xia
Juanjuan Xie
Mingqiang Fu
Danbo Lu
Yuan Wu
Huali Shen
Pengyuan Yang
Juying Qian
author_facet Ling Lin
Shanshan Liu
Zhangwei Chen
Yan Xia
Juanjuan Xie
Mingqiang Fu
Danbo Lu
Yuan Wu
Huali Shen
Pengyuan Yang
Juying Qian
author_sort Ling Lin
collection DOAJ
description Abstract Dilated cardiomyopathy (DCM), as characterized by the left ventricular dilatation and contractile dysfunction, is one of the molecular mechanisms of which are largely unexplored. Here, we profiled the region‐resolved transcriptome and proteome of healthy and DCM human myocardial tissue and obtained the deep‐coverage dataset consisting 7,605 proteins and 19,880 transcripts in four chambers of the human heart. On the basis of the core proteome and transcriptome characters of the healthy hearts, chamber‐specific proteome alterations were further revealed in end‐stage DCM, among which extracellular matrix (ECM), mitochondrial function, and muscle contraction were the most dysregulated biological processes. Protein–protein interaction network demonstrated divergent functional networks of DCM atrium and ventricle. Additionally, a 4‐biomarker panel (CTSB, vWF, C9, and MFGE8) was established with promising diagnostic potential for the DCM. Collectively, our data provide a global proteomic basis of the chamber‐specific cardiac tissue, and establish a protein catalog that holds promise for better definition and diagnosis of DCM.
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spelling doaj.art-bb075c6763e24b08a91d180b65e9b6c32023-02-21T16:13:55ZengWileyView2688-39882688-268X2023-02-0141n/an/a10.1002/VIW.20220040Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathyLing Lin0Shanshan Liu1Zhangwei Chen2Yan Xia3Juanjuan Xie4Mingqiang Fu5Danbo Lu6Yuan Wu7Huali Shen8Pengyuan Yang9Juying Qian10Institutes of Biomedical Sciences of Shanghai Medical School & Minhang Hospital Fudan University Shanghai ChinaInstitutes of Biomedical Sciences of Shanghai Medical School & Minhang Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaInstitutes of Biomedical Sciences of Shanghai Medical School & Minhang Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaInstitutes of Biomedical Sciences of Shanghai Medical School & Minhang Hospital Fudan University Shanghai ChinaInstitutes of Biomedical Sciences of Shanghai Medical School & Minhang Hospital Fudan University Shanghai ChinaDepartment of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai ChinaAbstract Dilated cardiomyopathy (DCM), as characterized by the left ventricular dilatation and contractile dysfunction, is one of the molecular mechanisms of which are largely unexplored. Here, we profiled the region‐resolved transcriptome and proteome of healthy and DCM human myocardial tissue and obtained the deep‐coverage dataset consisting 7,605 proteins and 19,880 transcripts in four chambers of the human heart. On the basis of the core proteome and transcriptome characters of the healthy hearts, chamber‐specific proteome alterations were further revealed in end‐stage DCM, among which extracellular matrix (ECM), mitochondrial function, and muscle contraction were the most dysregulated biological processes. Protein–protein interaction network demonstrated divergent functional networks of DCM atrium and ventricle. Additionally, a 4‐biomarker panel (CTSB, vWF, C9, and MFGE8) was established with promising diagnostic potential for the DCM. Collectively, our data provide a global proteomic basis of the chamber‐specific cardiac tissue, and establish a protein catalog that holds promise for better definition and diagnosis of DCM.https://doi.org/10.1002/VIW.20220040dilated cardiomyopathy, heart chambersproteome, serum biomarker panel, transcriptome
spellingShingle Ling Lin
Shanshan Liu
Zhangwei Chen
Yan Xia
Juanjuan Xie
Mingqiang Fu
Danbo Lu
Yuan Wu
Huali Shen
Pengyuan Yang
Juying Qian
Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
View
dilated cardiomyopathy, heart chambers
proteome, serum biomarker panel, transcriptome
title Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
title_full Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
title_fullStr Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
title_full_unstemmed Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
title_short Anatomically resolved transcriptome and proteome landscapes reveal disease‐relevant molecular signatures and systematic changes in heart function of end‐stage dilated cardiomyopathy
title_sort anatomically resolved transcriptome and proteome landscapes reveal disease relevant molecular signatures and systematic changes in heart function of end stage dilated cardiomyopathy
topic dilated cardiomyopathy, heart chambers
proteome, serum biomarker panel, transcriptome
url https://doi.org/10.1002/VIW.20220040
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