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Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study

Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq stu...

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Autores principales: Vancheri, Chiara, Morini, Elena, Prandi, Francesca Romana, Alkhoury, Elie, Celotto, Roberto, Romeo, Francesco, Novelli, Giuseppe, Amati, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234100/
https://www.ncbi.nlm.nih.gov/pubmed/34205376
http://dx.doi.org/10.3390/genes12060939
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author Vancheri, Chiara
Morini, Elena
Prandi, Francesca Romana
Alkhoury, Elie
Celotto, Roberto
Romeo, Francesco
Novelli, Giuseppe
Amati, Francesca
author_facet Vancheri, Chiara
Morini, Elena
Prandi, Francesca Romana
Alkhoury, Elie
Celotto, Roberto
Romeo, Francesco
Novelli, Giuseppe
Amati, Francesca
author_sort Vancheri, Chiara
collection PubMed
description Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq study on PBMCs from CAD patients and control subjects (CTR) and observed 113 differentially regulated AS events (24 up and 89 downregulated) in 86 genes. The RECK (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene was further analyzed in a larger case study (24 CTR subjects, 72 CAD and 32 AMI patients) for its Splicing-Index FC (FC = −2.64; p = 0.0217), the AS event involving an exon (exon 18), and its role in vascular inflammation and remodeling. We observed a significant downregulation of Long RECK splice variant (containing exon 18) in PBMCs of AMI compared to CTR subjects (FC = −3.3; p < 0.005). Interestingly, the Short RECK splice variant (lacking exon 18) was under-expressed in AMI compared to both CTR (FC = −4.5; p < 0.0001) and CAD patients (FC = −4.2; p < 0.0001). A ROC curve, constructed combining Long and Short RECK expression data, shows an AUC = 0.81 (p < 0.001) to distinguish AMI from stable CAD patients. A significant negative correlation between Long RECK and triglycerides in CTR group and a positive correlation in the AMI group was found. The combined evaluation of Long and Short RECK expression levels is a potential genomic biomarker for the discrimination of AMI from CAD patients. Our results underline the relevance of deeper studies on the expression of these two splice variants to elucidate their functional role in CAD development and progression.
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spelling pubmed-82341002021-06-27 Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study Vancheri, Chiara Morini, Elena Prandi, Francesca Romana Alkhoury, Elie Celotto, Roberto Romeo, Francesco Novelli, Giuseppe Amati, Francesca Genes (Basel) Article Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq study on PBMCs from CAD patients and control subjects (CTR) and observed 113 differentially regulated AS events (24 up and 89 downregulated) in 86 genes. The RECK (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene was further analyzed in a larger case study (24 CTR subjects, 72 CAD and 32 AMI patients) for its Splicing-Index FC (FC = −2.64; p = 0.0217), the AS event involving an exon (exon 18), and its role in vascular inflammation and remodeling. We observed a significant downregulation of Long RECK splice variant (containing exon 18) in PBMCs of AMI compared to CTR subjects (FC = −3.3; p < 0.005). Interestingly, the Short RECK splice variant (lacking exon 18) was under-expressed in AMI compared to both CTR (FC = −4.5; p < 0.0001) and CAD patients (FC = −4.2; p < 0.0001). A ROC curve, constructed combining Long and Short RECK expression data, shows an AUC = 0.81 (p < 0.001) to distinguish AMI from stable CAD patients. A significant negative correlation between Long RECK and triglycerides in CTR group and a positive correlation in the AMI group was found. The combined evaluation of Long and Short RECK expression levels is a potential genomic biomarker for the discrimination of AMI from CAD patients. Our results underline the relevance of deeper studies on the expression of these two splice variants to elucidate their functional role in CAD development and progression. MDPI 2021-06-19 /pmc/articles/PMC8234100/ /pubmed/34205376 http://dx.doi.org/10.3390/genes12060939 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vancheri, Chiara
Morini, Elena
Prandi, Francesca Romana
Alkhoury, Elie
Celotto, Roberto
Romeo, Francesco
Novelli, Giuseppe
Amati, Francesca
Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title_full Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title_fullStr Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title_full_unstemmed Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title_short Two RECK Splice Variants (Long and Short) Are Differentially Expressed in Patients with Stable and Unstable Coronary Artery Disease: A Pilot Study
title_sort two reck splice variants (long and short) are differentially expressed in patients with stable and unstable coronary artery disease: a pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234100/
https://www.ncbi.nlm.nih.gov/pubmed/34205376
http://dx.doi.org/10.3390/genes12060939
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