Transection of the cervical sympathetic trunk ameliorates pulmonary arterial hypertension by reprogramming transcription factor networks and alternative splicing in rat model
- 1Department of Cardiology, General Hospital of Ningxia Medical University
- 2Department of Anesthesiology, General Hospital of Ningxia Medical University
Abstract
Background: Transection of the cervical sympathetic trunk (TCST) ameliorates pulmonary arterial hypertension (PAH), but the molecular mechanisms remain unclear. This study aimed to elucidate these mechanisms in monocrotaline (MCT)-induced PAH rats through transcriptomic profiling.
Methods: PAH rats were divided into control, PAH, PAH + sham, and PAH + TCST groups. Therapeutic effects were evaluated by hemodynamics and histology. RNA-seq was performed on lung tissues to identify differentially expressed genes (DEGs), followed by transcription factor (TF) network analysis and alternative splicing analysis, with validation by qPCR and ELISA.
Results: TCST significantly reduced mPAP, RVSP, and RVHI, and attenuated vascular remodeling. RNA-seq identified 500 DEGs (61 upregulated, 439 downregulated). TF network analysis revealed that target genes of differentially expressed TFs were enriched in inflammation, proliferation, and calcium signaling. Multiple PAH-associated genes ( Bmp2 , Ptgs2 , Cxcl13, Wnt7b , Tacr1 , Adra1d ) were downregulated following TCST. Alternative splicing analysis showed that TCST modulated RNA-binding protein (RBP) expression and altered splicing patterns of PAH-relevant genes ( Aldh2 , Il1rn , Foxm1 ). qPCR and ELISA confirmed suppression of the Foxa3 / Adra1d - Tacr1 axis and reduced IP3 production.
Conclusions: TCST exerts therapeutic effects through selective reprogramming of TF networks and regulation of RBP-mediated alternative splicing, coordinately suppressing PAH-associated pathways at transcriptional and post-transcriptional levels. These findings provide mechanistic insights and a theoretical basis for developing neuromodulatory strategies for PAH.
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BibTeX
@article{hao2026transection,
title = {{Transection of the cervical sympathetic trunk ameliorates pulmonary arterial hypertension by reprogramming transcription factor networks and alternative splicing in rat model}},
author = {Yu Hao and Peipei Li and Hua Cheng and Ning Yan and Hui Zhang and Xueping Ma},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1967847},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1967847/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transection of the cervical sympathetic trunk ameliorates pulmonary arterial hypertension by reprogramming transcription factor networks and alternative splicing in rat model
AU - Yu Hao
AU - Peipei Li
AU - Hua Cheng
AU - Ning Yan
AU - Hui Zhang
AU - Xueping Ma
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1967847
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1967847/full
AB - Background: Transection of the cervical sympathetic trunk (TCST) ameliorates pulmonary arterial hypertension (PAH), but the molecular mechanisms remain unclear. This study aimed to elucidate these mechanisms in monocrotaline (MCT)-induced PAH rats through transcriptomic profiling. Methods: PAH rats were divided into control, PAH, PAH + sham, and PAH + TCST groups. Therapeutic effects were evaluated by hemodynamics and histology. RNA-seq was performed on lung tissues to identify differentially expressed genes (DEGs), followed by transcription factor (TF) network analysis and alternative splicing analysis, with validation by qPCR and ELISA. Results: TCST significantly reduced mPAP, RVSP, and RVHI, and attenuated vascular remodeling. RNA-seq identified 500 DEGs (61 upregulated, 439 downregulated). TF network analysis revealed that target genes of differentially expressed TFs were enriched in inflammation, proliferation, and calcium signaling. Multiple PAH-associated genes ( Bmp2 , Ptgs2 , Cxcl13, Wnt7b , Tacr1 , Adra1d ) were downregulated following TCST. Alternative splicing analysis showed that TCST modulated RNA-binding protein (RBP) expression and altered splicing patterns of PAH-relevant genes ( Aldh2 , Il1rn , Foxm1 ). qPCR and ELISA confirmed suppression of the Foxa3 / Adra1d - Tacr1 axis and reduced IP3 production. Conclusions: TCST exerts therapeutic effects through selective reprogramming of TF networks and regulation of RBP-mediated alternative splicing, coordinately suppressing PAH-associated pathways at transcriptional and post-transcriptional levels. These findings provide mechanistic insights and a theoretical basis for developing neuromodulatory strategies for PAH.
SN - 2297-055X
ER -