| Autor: |
Bobos D; Department of Pediatric Cardiothoracic Surgery, Onassis Cardiac Surgery Center, 17674 Athens, Greece., Soufla G; Department of Hematology and Blood Transfusion, Onassis Cardiac Surgery Center, 17674 Athens, Greece., Angouras DC; Department of Cardiac Surgery, Faculty of Medicine, Attikon University Hospital, National Kapodistrian University of Athens, 15771 Athens, Greece., Lekakis I; Second Department of Cardiology, Attikon Hospital, Athens Medical School, National Kapodistrian University of Athens, 15771 Athens, Greece., Georgopoulos S; First Department of Surgery, Laikon General Hospital, Medical School, National Kapodistrian University of Athens, 15771 Athens, Greece., Melissari E; Department of Hematology and Blood Transfusion, Onassis Cardiac Surgery Center, 17674 Athens, Greece. |
| Abstrakt: |
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. |
