Postnatal Right Ventricular Developmental Track Changed by Volume Overload

Background Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava...

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Main Authors: Sijuan Sun, Yuqing Hu, Yingying Xiao, Shoubao Wang, Chuan Jiang, Jinfen Liu, Hao Zhang, Haifa Hong, Fen Li, Lincai Ye
Format: Article
Language:English
Published: Wiley 2021-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.121.020854
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author Sijuan Sun
Yuqing Hu
Yingying Xiao
Shoubao Wang
Chuan Jiang
Jinfen Liu
Hao Zhang
Haifa Hong
Fen Li
Lincai Ye
author_facet Sijuan Sun
Yuqing Hu
Yingying Xiao
Shoubao Wang
Chuan Jiang
Jinfen Liu
Hao Zhang
Haifa Hong
Fen Li
Lincai Ye
author_sort Sijuan Sun
collection DOAJ
description Background Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava on postnatal day 7 and confirmed by abdominal ultrasound, echocardiography, and hematoxylin and eosin staining. The RNA‐sequencing results showed that the top 5 most enriched gene ontology terms in normal RV development were energy derivation by oxidation of organic compounds, generation of precursor metabolites and energy, cellular respiration, striated muscle tissue development, and muscle organ development. Under the influence of VO, the top 5 most enriched gene ontology terms were angiogenesis, regulation of cytoskeleton organization, regulation of vasculature development, regulation of mitotic cell cycle, and regulation of the actin filament‐based process. The top 3 enriched signaling pathways for the normal RV development were PPAR signaling pathway, citrate cycle (Tricarboxylic acid cycle), and fatty acid degradation. VO changed the signaling pathways to focal adhesion, the PI3K‐Akt signaling pathway, and pathways in cancer. The RNA sequencing results were confirmed by the examination of the markers of metabolic and cardiac muscle maturation and the markers of cell cycle and angiogenesis. Conclusions A neonatal mouse VO model was successfully established, and the main processes of postnatal RV development were metabolic and cardiac muscle maturation, and VO changed that to angiogenesis and cell cycle regulation.
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spelling doaj.art-0bb1118a8a924178953dec3a0b101ab12023-06-06T12:10:51ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-08-01101610.1161/JAHA.121.020854Postnatal Right Ventricular Developmental Track Changed by Volume OverloadSijuan Sun0Yuqing Hu1Yingying Xiao2Shoubao Wang3Chuan Jiang4Jinfen Liu5Hao Zhang6Haifa Hong7Fen Li8Lincai Ye9Department of Pediatric Intensive Care Unit Shanghai Children's Medical Center School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Cardiology, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaShanghai Institute for Pediatric Congenital Heart Disease Shanghai Children's Medical Center School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Cardiology, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaBackground Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava on postnatal day 7 and confirmed by abdominal ultrasound, echocardiography, and hematoxylin and eosin staining. The RNA‐sequencing results showed that the top 5 most enriched gene ontology terms in normal RV development were energy derivation by oxidation of organic compounds, generation of precursor metabolites and energy, cellular respiration, striated muscle tissue development, and muscle organ development. Under the influence of VO, the top 5 most enriched gene ontology terms were angiogenesis, regulation of cytoskeleton organization, regulation of vasculature development, regulation of mitotic cell cycle, and regulation of the actin filament‐based process. The top 3 enriched signaling pathways for the normal RV development were PPAR signaling pathway, citrate cycle (Tricarboxylic acid cycle), and fatty acid degradation. VO changed the signaling pathways to focal adhesion, the PI3K‐Akt signaling pathway, and pathways in cancer. The RNA sequencing results were confirmed by the examination of the markers of metabolic and cardiac muscle maturation and the markers of cell cycle and angiogenesis. Conclusions A neonatal mouse VO model was successfully established, and the main processes of postnatal RV development were metabolic and cardiac muscle maturation, and VO changed that to angiogenesis and cell cycle regulation.https://www.ahajournals.org/doi/10.1161/JAHA.121.020854cardiomyocyteproliferationright ventricleRNA sequencingvolume overload
spellingShingle Sijuan Sun
Yuqing Hu
Yingying Xiao
Shoubao Wang
Chuan Jiang
Jinfen Liu
Hao Zhang
Haifa Hong
Fen Li
Lincai Ye
Postnatal Right Ventricular Developmental Track Changed by Volume Overload
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiomyocyte
proliferation
right ventricle
RNA sequencing
volume overload
title Postnatal Right Ventricular Developmental Track Changed by Volume Overload
title_full Postnatal Right Ventricular Developmental Track Changed by Volume Overload
title_fullStr Postnatal Right Ventricular Developmental Track Changed by Volume Overload
title_full_unstemmed Postnatal Right Ventricular Developmental Track Changed by Volume Overload
title_short Postnatal Right Ventricular Developmental Track Changed by Volume Overload
title_sort postnatal right ventricular developmental track changed by volume overload
topic cardiomyocyte
proliferation
right ventricle
RNA sequencing
volume overload
url https://www.ahajournals.org/doi/10.1161/JAHA.121.020854
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