Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery dis...

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Main Authors: Francisco Rodríguez-Esparragón, Laura B. Torres-Mata, Sara E. Cazorla-Rivero, Jaime A. Serna Gómez, Jesús M. González Martín, Ángeles Cánovas-Molina, José A. Medina-Suárez, Ayose N. González-Hernández, Lidia Estupiñán-Quintana, María C. Bartolomé-Durán, José C. Rodríguez-Pérez, Bernardino Clavo Varas
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/22/16127
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author Francisco Rodríguez-Esparragón
Laura B. Torres-Mata
Sara E. Cazorla-Rivero
Jaime A. Serna Gómez
Jesús M. González Martín
Ángeles Cánovas-Molina
José A. Medina-Suárez
Ayose N. González-Hernández
Lidia Estupiñán-Quintana
María C. Bartolomé-Durán
José C. Rodríguez-Pérez
Bernardino Clavo Varas
author_facet Francisco Rodríguez-Esparragón
Laura B. Torres-Mata
Sara E. Cazorla-Rivero
Jaime A. Serna Gómez
Jesús M. González Martín
Ángeles Cánovas-Molina
José A. Medina-Suárez
Ayose N. González-Hernández
Lidia Estupiñán-Quintana
María C. Bartolomé-Durán
José C. Rodríguez-Pérez
Bernardino Clavo Varas
author_sort Francisco Rodríguez-Esparragón
collection DOAJ
description ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.
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spelling doaj.art-d1848ab3ae414580b430c9fd4e82fa232023-11-24T14:46:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221612710.3390/ijms242216127Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery DiseaseFrancisco Rodríguez-Esparragón0Laura B. Torres-Mata1Sara E. Cazorla-Rivero2Jaime A. Serna Gómez3Jesús M. González Martín4Ángeles Cánovas-Molina5José A. Medina-Suárez6Ayose N. González-Hernández7Lidia Estupiñán-Quintana8María C. Bartolomé-Durán9José C. Rodríguez-Pérez10Bernardino Clavo Varas11Research Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainVice Chancellor of Research, Universidad Fernando Pessoa Canarias, 35002 Santa María de Guía de Gran Canaria, Gran Canaria, SpainResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrín, 35010 Las Palmas de Gran Canaria, Gran Canaria, SpainANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.https://www.mdpi.com/1422-0067/24/22/16127CDKN2B-AS1 (ANRIL)CDKN2AVEGFKDRcardiovascular riskcoronary artery disease
spellingShingle Francisco Rodríguez-Esparragón
Laura B. Torres-Mata
Sara E. Cazorla-Rivero
Jaime A. Serna Gómez
Jesús M. González Martín
Ángeles Cánovas-Molina
José A. Medina-Suárez
Ayose N. González-Hernández
Lidia Estupiñán-Quintana
María C. Bartolomé-Durán
José C. Rodríguez-Pérez
Bernardino Clavo Varas
Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
International Journal of Molecular Sciences
CDKN2B-AS1 (ANRIL)
CDKN2A
VEGF
KDR
cardiovascular risk
coronary artery disease
title Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
title_full Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
title_fullStr Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
title_full_unstemmed Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
title_short Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease
title_sort analysis of anril isoforms and key genes in patients with severe coronary artery disease
topic CDKN2B-AS1 (ANRIL)
CDKN2A
VEGF
KDR
cardiovascular risk
coronary artery disease
url https://www.mdpi.com/1422-0067/24/22/16127
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