右心室容量超负荷通过免疫反应重新启动心肌细胞增殖。

Right ventricular volume overload reboots cardiomyocyte proliferation via immune responses.

机构信息

Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China.

Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Transl Med. 2024 Nov 28;22(1):1075. doi: 10.1186/s12967-024-05839-8.

DOI:10.1186/s12967-024-05839-8

PMID:39609689

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11604012/

Abstract

BACKGROUND

Right ventricular volume overload (RVVO) is one of the most important hemodynamic characteristics in children with congenital heart disease (CHD) and heart failure, and cardiomyocyte (CM) proliferation is one of the most vital factors for improving cardiac performance. However, whether and how RVVO reboots CM proliferation remains elusive.

METHODS AND RESULTS

We first created a neonatal RVVO mouse model via abdominal aorta and inferior vena cava-fistula microsurgery at postnatal day 7 (P7), the edge of CM proliferation window. We subsequently performed bulk RNA-seq, single cell RNA-seq/flow cytometry, and immunofluorescence staining on the right ventricles (RV) of RVVO mice at P14/P21, defined as prepubertal stage, revealing that RVVO temporarily reboots prepubertal CM proliferation via immune responses.

CONCLUSIONS

In considering the importance of RVVO and CM proliferation, this study may bring an opportunity to create a novel paradigm to treat pediatric CHDs or heart failure.

摘要

背景

右心室容量超负荷（RVVO）是儿童先天性心脏病（CHD）和心力衰竭最重要的血流动力学特征之一，心肌细胞（CM）增殖是改善心功能的最重要因素之一。然而，RVVO 是否以及如何重新启动 CM 增殖仍然难以捉摸。

方法和结果

我们首先在出生后第 7 天（P7）通过腹主动脉和下腔静脉吻合术创建了一种新生 RVVO 小鼠模型，该模型处于 CM 增殖窗口的边缘。随后，我们对 P14/P21 的 RVVO 小鼠的右心室（RV）进行了批量 RNA-seq、单细胞 RNA-seq/流式细胞术和免疫荧光染色，该阶段定义为青春期前阶段，结果表明 RVVO 通过免疫反应暂时重新启动青春期前的 CM 增殖。