Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload.
Cell Death Discov
; 7(1): 208, 2021 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-34365468
ABSTRACT
The molecular atlas of postnatal mouse ventricular development has been made available and cardiac regeneration is documented to be a downregulated process. The right ventricle (RV) differs from the left ventricle. How volume overload (VO), a common pathologic state in children with congenital heart disease, affects the downregulated processes of the RV is currently unclear. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 7 (P7) using a mouse model to induce a prepubertal RV VO. RNAseq analysis of RV (from postnatal day 14 to 21) demonstrated that angiogenesis was the most enriched gene ontology (GO) term in both the sham and VO groups. Regulation of the mitotic cell cycle was the second-most enriched GO term in the VO group but it was not in the list of enriched GO terms in the sham group. In addition, the number of Ki67-positive cardiomyocytes increased approximately 20-fold in the VO group compared to the sham group. The intensity of the vascular endothelial cells also changed dramatically over time in both groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the downregulated transcriptome revealed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway was replaced by the cell cycle in the top-20 enriched KEGG terms because of the VO. Angiogenesis was one of the primary downregulated processes in postnatal RV development, and the cell cycle was reactivated under the influence of VO. The mechanism underlying the effects we observed may be associated with the replacement of the PPAR-signaling pathway with the cell-cycle pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Death Discov
Ano de publicação:
2021
Tipo de documento:
Article