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Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease

Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing ana...

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Autores principales: Bobos, Dimitrios, Soufla, Giannoula, Angouras, Dimitrios C., Lekakis, Ioannis, Georgopoulos, Sotirios, Melissari, Euthemia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10453726/
https://www.ncbi.nlm.nih.gov/pubmed/37627976
http://dx.doi.org/10.3390/diagnostics13162717
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author Bobos, Dimitrios
Soufla, Giannoula
Angouras, Dimitrios C.
Lekakis, Ioannis
Georgopoulos, Sotirios
Melissari, Euthemia
author_facet Bobos, Dimitrios
Soufla, Giannoula
Angouras, Dimitrios C.
Lekakis, Ioannis
Georgopoulos, Sotirios
Melissari, Euthemia
author_sort Bobos, Dimitrios
collection PubMed
description Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation.
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spelling pubmed-104537262023-08-26 Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease Bobos, Dimitrios Soufla, Giannoula Angouras, Dimitrios C. Lekakis, Ioannis Georgopoulos, Sotirios Melissari, Euthemia Diagnostics (Basel) Article Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation. MDPI 2023-08-21 /pmc/articles/PMC10453726/ /pubmed/37627976 http://dx.doi.org/10.3390/diagnostics13162717 Text en © 2023 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
Bobos, Dimitrios
Soufla, Giannoula
Angouras, Dimitrios C.
Lekakis, Ioannis
Georgopoulos, Sotirios
Melissari, Euthemia
Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title_full Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title_fullStr Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title_full_unstemmed Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title_short Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease
title_sort investigation of the role of bmp2 and -4 in asd, vsd and complex congenital heart disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10453726/
https://www.ncbi.nlm.nih.gov/pubmed/37627976
http://dx.doi.org/10.3390/diagnostics13162717
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