Single nucleus transcriptome of a "Super RV" shows increased insulin and angiogenesis signaling.
Single nucleus transcriptome of a "Super RV" shows increased insulin and angiogenesis signaling.
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“超级 RV”的单核转录组显示胰岛素和血管生成信号增加。
DOI：
10.1101/2023.11.28.569092
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Martin,James
中科院分区：
文献类型：
--
作者：
Turaga,Diwakar;Li,Xiao;Zhao,Yi;Tsai,Chang-Ru;Moreira,Axel;Hickey,Edward;Adachi,Iki;Martin,James
右室(RV)是心脏的四个泵室之一，将血液输送到肺部。在严重的先天性心脏病和肺动脉高压中，RV被泵入体循环。这类全身性房车通常会因为压力过载而出现早期故障。在极少数情况下，全身性房车会持续到后来的几十年--通俗地说，就是“超级房车”。在这里，我们展示了一位60岁的先天性矫正性大动脉转位(CCTGA)患者的系统性RV的单核转录组。我们的数据显示有两条特定的信号通路在CCTGA RV心肌中丰富。首先，我们发现胰岛素样生长因子(IGF1)信号在系统性右室心肌中增加：主要受体IGFR1在心肌细胞中表达增加，IGF1配体在心脏成纤维细胞和巨噬细胞中表达增加。其次，我们发现心肌细胞中VEGF和WNT9配体的表达增加，内皮细胞中VEGF1R和WNT9受体的表达增加，这与血管生成有关。我们表明，增加胰岛素和血管生成信号是RV对增加的压力超负荷的潜在有利的适应。这项对成人全身性RV的研究为了解先天性心脏病和肺动脉高压时RV对全身压力的重塑提供了重要的框架。
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.