一个“超级RV”的单核转录组显示胰岛素和血管生成信号增加。

Single nucleus transcriptome of a "Super RV" shows increased insulin and angiogenesis signaling.

作者信息

Turaga Diwakar, Li Xiao, Zhao Yi, Tsai Chang-Ru, Moreira Axel, Hickey Edward, Adachi Iki, Martin James

机构信息

Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

Division of Critical Care Medicine, Texas Children's Hospital, Houston TX, USA.

出版信息

bioRxiv. 2024 Jan 3:2023.11.28.569092. doi: 10.1101/2023.11.28.569092.

Abstract

The right ventricle (RV) is one of the four pumping chambers of the heart, pumping blood to the lungs. In severe forms of congenital heart disease and pulmonary hypertension, the RV is made to pump into the systemic circulation. Such systemic RVs typically display early failure due to pressure overload. In rare cases a systemic RV persists into later decades of life - colloquially called a 'Super RV'. Here we present the single-nucleus transcriptome of a systemic RV from a 60-year-old with congenitally corrected transposition of great arteries (ccTGA). Our data shows two specific signaling pathways enriched in the ccTGA RV myocardium. First, we show increased insulin like growth factor (IGF1) signaling within the systemic RV myocardium: there is increased expression of the main receptor IGFR1 within the cardiomyocytes, and IGF1 ligands within the cardiofibroblasts and macrophages. Second, we find increased VEGF and Wnt9 ligand expression in cardiomyocytes and increased VEGF1R and Wnt9 receptors in endothelial cells, which are implicated in angiogenesis. We show that increased insulin and angiogenesis signaling are potentially beneficial RV adaptations to increased pressure overload. This study of an adult systemic RV provides an important framework for understanding RV remodeling to systemic pressures in congenital heart disease and pulmonary hypertension.

摘要

右心室(RV)是心脏的四个泵血腔室之一,负责将血液泵入肺部。在严重的先天性心脏病和肺动脉高压病例中,右心室被迫将血液泵入体循环。这种体循环右心室通常会因压力过载而早期衰竭。在罕见情况下,体循环右心室可存续至生命的后几十年,通俗地称为“超级右心室”。在此,我们展示了一名60岁患有大动脉转位矫正型(ccTGA)患者的体循环右心室的单核转录组。我们的数据显示,ccTGA右心室心肌中富集了两条特定的信号通路。首先,我们发现体循环右心室心肌内胰岛素样生长因子(IGF1)信号增强:心肌细胞内主要受体IGFR1的表达增加,成纤维细胞和巨噬细胞内IGF1配体增加。其次,我们发现心肌细胞中VEGF和Wnt9配体表达增加,内皮细胞中VEGF1R和Wnt9受体增加,这些都与血管生成有关。我们表明,胰岛素信号增强和血管生成信号增强可能是右心室对压力过载增加的有益适应性变化。这项对成人体循环右心室的研究为理解先天性心脏病和肺动脉高压中右心室对体循环压力的重塑提供了重要框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6648/10775419/ad8aa006ef79/nihpp-2023.11.28.569092v3-f0001.jpg

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