Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload
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 congeni...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-021-00593-y |
| _version_ | 1818357763687841792 |
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| author | Chunxia Zhou Sijuan Sun Mengyu Hu Yingying Xiao Xiafeng Yu Lincai Ye Lisheng Qiu |
| author_facet | Chunxia Zhou Sijuan Sun Mengyu Hu Yingying Xiao Xiafeng Yu Lincai Ye Lisheng Qiu |
| author_sort | Chunxia Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T20:18:17Z |
| format | Article |
| id | doaj.art-a852ed000fee4607a5bb1568b10254df |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-13T20:18:17Z |
| publishDate | 2021-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-a852ed000fee4607a5bb1568b10254df2022-12-21T23:32:46ZengNature Publishing GroupCell Death Discovery2058-77162021-08-017111010.1038/s41420-021-00593-yDownregulated developmental processes in the postnatal right ventricle under the influence of a volume overloadChunxia Zhou0Sijuan Sun1Mengyu Hu2Yingying Xiao3Xiafeng Yu4Lincai Ye5Lisheng Qiu6Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao tong UniversityBasic Medical School, Shangdong First Medical UniversityDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong UniversityAbstract 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.https://doi.org/10.1038/s41420-021-00593-y |
| spellingShingle | Chunxia Zhou Sijuan Sun Mengyu Hu Yingying Xiao Xiafeng Yu Lincai Ye Lisheng Qiu Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload Cell Death Discovery |
| title | Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| title_full | Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| title_fullStr | Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| title_full_unstemmed | Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| title_short | Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| title_sort | downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload |
| url | https://doi.org/10.1038/s41420-021-00593-y |
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