Evidence map›Paper›PMID 41673666›Full record

ArticleRespiratory research2026

Multi-omics integration study of vascular smooth muscle cell phenotypic conversion identified novel biomarkers in idiopathic pulmonary arterial hypertension.

Ruhao Wu, Ke Wang, Mingwei Fan, Ruohan Jia, Yuanying Ma, Congying Yuan, Meichen Yu, Mingzhou Guo, Tianci Jiang, Yu Wang and 5 more

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Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Ruhao Wu *Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Ke Wang *Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Mingwei FanDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Ruohan JiaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yuanying MaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Congying YuanDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Meichen YuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Mingzhou GuoDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Tianci JiangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yu WangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yue LiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Pengfei LiDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yichen LiuDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Youyou GongDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Zhe ChengDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. fccchengzhe@zzu.edu.cn.

Funding

Key Scientific Research Project of Science and Technology Department of Henan Province 231111310800National Natural Science Foundation of China 82170037
6 · The paper itself

Abstract

backgroundIdiopathic pulmonary arterial hypertension (IPAH) is a progressive, high‑mortality disease driven in part by maladaptive vascular remodeling. Phenotypic conversion of vascular smooth muscle cells (VSMCs) is implicated in this process, but the cellular heterogeneity and regulatory drivers in IPAH remain incompletely defined.

methodsWe integrated scRNA‑seq datasets from IPAH and control lungs samples with bulk RNA‑seq from IPAH patients, MCT‑induced rat IPAH models, applying diffusion‑map dimensionality reduction, pseudotime inference, CellChat, and machine learning to nominate phenotypic conversion regulatory genes (PCRGs). Candidate genes were validated in independent cohorts and functionally tested in hypoxia‑induced human PASMCs.

resultsSingle-cell analysis identified three VSMC clusters-contractile, proliferative, and synthetic-and reconstructed a dedifferentiation trajectory. 40 PCRGs correlated with the primary diffusion-map component, of which POSTN and CCDC80 emerged as hub genes up-regulated in rat and human IPAH cohorts. Hypoxia induced their expression in PASMCs, and siRNA knockdown attenuated hypoxia‑driven proliferation and migration. A multivariable VSMC phenotypic conversion signature (VPCS) integrating these biomarkers and clinical variables demonstrated robust diagnostic discrimination in validation datasets.

conclusionsOur from high‑dimensional datasets.integrative VSMC‑centered approach delineates dynamic state transitions in IPAH, nominates CCDC80 and POSTN as candidate regulators and biomarkers, and offers a practical framework for prioritizing targets

Indexed as

Familial Primary Pulmonary HypertensionMuscle, Smooth, VascularMyocytes, Smooth MuscleAnimalsBiomarkersCells, CulturedFemaleHumansMaleMultiomicsPhenotypeRatsRats, Sprague-DawleyBiomarkersIdiopathic pulmonary arterial hypertensionMulti-omicsPhenotypic conversionVascular smooth muscle cells

Identifiers

PMID41673666
PMCPMC12997889

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.