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<p>The mechanism underlying vascular remodeling in pulmonary arterial hypertension (PAH) involves complex interactions among various cell types, with dysregulation of endothelial cells (ECs) homeostasis considered a crucial pathological factor. However, their local cellular changes still need to be fully identified during PAH. This study utilized single-cell RNA sequencing data from the GEO database to analyze lung tissue samples from PAH patients and normal controls, revealing significant heterogeneity in lung ECs and dysregulated metabolic pathways. We identified a significant expansion of capillary ECs in PAH patients, linked to dysregulated angiogenesis and glycolysis-tricarboxylic acid cycle metabolic pathways. Through integrative high-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning, we identified SPRY1 as a novel key biomarker in PAH pathogenesis and validated its significant downregulation in a monocrotaline-induced PAH rat model. These findings establish capillary ECs expansion and SPRY1 deficiency as pivotal drivers in PAH pathogenesis, providing a foundation for precise therapeutic targeting.</p> Graphical abstract <p></p>

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Endothelial SPRY1 deficiency associates with angiogenic-metabolic reprogramming in pulmonary arterial hypertension: a multi-omics analysis of bulk and single-cell transcriptomic profiles

  • 期刊论文

  • 发表日期：

    2025年9月26日

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  • Yanfei Mo,
  • Desheng Wang,
  • Zhenkun Deng,
  • Pingping Zhao,
  • Zhen Gou,
  • Xiaoyun Sun,
  • Yunrui Zhang,
  • Yang Bai

摘要

The mechanism underlying vascular remodeling in pulmonary arterial hypertension (PAH) involves complex interactions among various cell types, with dysregulation of endothelial cells (ECs) homeostasis considered a crucial pathological factor. However, their local cellular changes still need to be fully identified during PAH. This study utilized single-cell RNA sequencing data from the GEO database to analyze lung tissue samples from PAH patients and normal controls, revealing significant heterogeneity in lung ECs and dysregulated metabolic pathways. We identified a significant expansion of capillary ECs in PAH patients, linked to dysregulated angiogenesis and glycolysis-tricarboxylic acid cycle metabolic pathways. Through integrative high-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning, we identified SPRY1 as a novel key biomarker in PAH pathogenesis and validated its significant downregulation in a monocrotaline-induced PAH rat model. These findings establish capillary ECs expansion and SPRY1 deficiency as pivotal drivers in PAH pathogenesis, providing a foundation for precise therapeutic targeting.

Graphical abstract