Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage

Background: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV...

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Autores principales: Qing Cui, Sijuan Sun, Hongbin Zhu, Yingying Xiao, Chuan Jiang, Hao Zhang, Jinfen Liu, Lincai Ye, Jie Shen
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/e40d0ca436b046e1a46a3f8abe2289af
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spelling oai:doaj.org-article:e40d0ca436b046e1a46a3f8abe2289af2021-11-16T05:43:00ZVolume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage2297-055X10.3389/fcvm.2021.772336https://doaj.org/article/e40d0ca436b046e1a46a3f8abe2289af2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.772336/fullhttps://doaj.org/toc/2297-055XBackground: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF.Methods and Results: We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group.Conclusions: A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.Qing CuiSijuan SunHongbin ZhuYingying XiaoChuan JiangHao ZhangHao ZhangJinfen LiuJinfen LiuLincai YeLincai YeLincai YeJie ShenFrontiers Media S.A.articlevolume overloadRNA-seqtetralogy of Fallotratright ventricular (RV)Diseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic volume overload
RNA-seq
tetralogy of Fallot
rat
right ventricular (RV)
Diseases of the circulatory (Cardiovascular) system
RC666-701
spellingShingle volume overload
RNA-seq
tetralogy of Fallot
rat
right ventricular (RV)
Diseases of the circulatory (Cardiovascular) system
RC666-701
Qing Cui
Sijuan Sun
Hongbin Zhu
Yingying Xiao
Chuan Jiang
Hao Zhang
Hao Zhang
Jinfen Liu
Jinfen Liu
Lincai Ye
Lincai Ye
Lincai Ye
Jie Shen
Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
description Background: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF.Methods and Results: We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group.Conclusions: A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.
format article
author Qing Cui
Sijuan Sun
Hongbin Zhu
Yingying Xiao
Chuan Jiang
Hao Zhang
Hao Zhang
Jinfen Liu
Jinfen Liu
Lincai Ye
Lincai Ye
Lincai Ye
Jie Shen
author_facet Qing Cui
Sijuan Sun
Hongbin Zhu
Yingying Xiao
Chuan Jiang
Hao Zhang
Hao Zhang
Jinfen Liu
Jinfen Liu
Lincai Ye
Lincai Ye
Lincai Ye
Jie Shen
author_sort Qing Cui
title Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
title_short Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
title_full Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
title_fullStr Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
title_full_unstemmed Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage
title_sort volume overload initiates an immune response in the right ventricle at the neonatal stage
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e40d0ca436b046e1a46a3f8abe2289af
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