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Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis

Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therape...

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Detalles Bibliográficos
Autores principales: Alimadadi, Ahmad, Aryal, Sachin, Manandhar, Ishan, Joe, Bina, Cheng, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278960/
https://www.ncbi.nlm.nih.gov/pubmed/32423033
http://dx.doi.org/10.3390/ijms21103472
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author Alimadadi, Ahmad
Aryal, Sachin
Manandhar, Ishan
Joe, Bina
Cheng, Xi
author_facet Alimadadi, Ahmad
Aryal, Sachin
Manandhar, Ishan
Joe, Bina
Cheng, Xi
author_sort Alimadadi, Ahmad
collection PubMed
description Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therapeutic strategies. In this study, we used four RNA-seq datasets from four different studies, including 41 ICM and 42 non-failing control (NF) samples of human left ventricle tissues, to perform the first RNA-seq meta-analysis in the field of clinical ICM, in order to identify important transcriptional regulators and their targeted genes involved in ICM. Our meta-analysis identified 911 differentially expressed genes (DEGs) with 582 downregulated and 329 upregulated. Interestingly, 54 new DEGs were detected only by meta-analysis but not in individual datasets. Upstream regulator analysis through Ingenuity Pathway Analysis (IPA) identified three key transcriptional regulators. TBX5 was identified as the only inhibited regulator (z-score = −2.89). F2R and SFRP4 were identified as the activated regulators (z-scores = 2.56 and 2.00, respectively). Multiple downstream genes regulated by TBX5, F2R, and SFRP4 were involved in ICM-related diseases such as HF and arrhythmia. Overall, our study is the first to perform an RNA-seq meta-analysis for clinical ICM and provides robust candidate genes, including three key transcriptional regulators, for future diagnostic and therapeutic applications in ischemic heart failure.
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spelling pubmed-72789602020-06-15 Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis Alimadadi, Ahmad Aryal, Sachin Manandhar, Ishan Joe, Bina Cheng, Xi Int J Mol Sci Article Ischemic cardiomyopathy (ICM), characterized by pre-existing myocardial infarction or severe coronary artery disease, is the major cause of heart failure (HF). Identification of novel transcriptional regulators in ischemic HF can provide important biomarkers for developing new diagnostic and therapeutic strategies. In this study, we used four RNA-seq datasets from four different studies, including 41 ICM and 42 non-failing control (NF) samples of human left ventricle tissues, to perform the first RNA-seq meta-analysis in the field of clinical ICM, in order to identify important transcriptional regulators and their targeted genes involved in ICM. Our meta-analysis identified 911 differentially expressed genes (DEGs) with 582 downregulated and 329 upregulated. Interestingly, 54 new DEGs were detected only by meta-analysis but not in individual datasets. Upstream regulator analysis through Ingenuity Pathway Analysis (IPA) identified three key transcriptional regulators. TBX5 was identified as the only inhibited regulator (z-score = −2.89). F2R and SFRP4 were identified as the activated regulators (z-scores = 2.56 and 2.00, respectively). Multiple downstream genes regulated by TBX5, F2R, and SFRP4 were involved in ICM-related diseases such as HF and arrhythmia. Overall, our study is the first to perform an RNA-seq meta-analysis for clinical ICM and provides robust candidate genes, including three key transcriptional regulators, for future diagnostic and therapeutic applications in ischemic heart failure. MDPI 2020-05-14 /pmc/articles/PMC7278960/ /pubmed/32423033 http://dx.doi.org/10.3390/ijms21103472 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alimadadi, Ahmad
Aryal, Sachin
Manandhar, Ishan
Joe, Bina
Cheng, Xi
Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title_full Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title_fullStr Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title_full_unstemmed Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title_short Identification of Upstream Transcriptional Regulators of Ischemic Cardiomyopathy Using Cardiac RNA-Seq Meta-Analysis
title_sort identification of upstream transcriptional regulators of ischemic cardiomyopathy using cardiac rna-seq meta-analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278960/
https://www.ncbi.nlm.nih.gov/pubmed/32423033
http://dx.doi.org/10.3390/ijms21103472
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