Progress on omics studies of chronic thromboembolic pulmonary hypertension

doi:10.16352/j.issn.1001-6325.2025.07.0963

Abstract

Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by unresolved thrombi and chronic embolization in the pulmonary arteries. In recent years, multi-omics technologies have provided multidimensional insights into CTEPH. Single-cell transcriptomics has identified key pathogenic cell subsets and related mechanisms; Genomics has revealed susceptibility genes associated with coagulation; Proteomics has uncovered differentially expressed proteins closely linked to vascular remodeling; And metabolomics has characterized metabolic reprogramming features and potential sub-typing biomarkers. This review summarizes recent advances in these omics fields and discusses their value and prospects in mechanistic exploration, biomarker discovery, and personalized therapeutic strategies.

Key words: chronic thromboembolic pulmonary hypertension(CTEPH), single-cell transcriptomics, genomics, proteomics, metabolomics

CLC Number:

R543.2

DUAN Wenxin, SONG Wanlu, YANG Peiran, WANG Jing. Progress on omics studies of chronic thromboembolic pulmonary hypertension[J]. Basic & Clinical Medicine, 2025, 45(7): 963-968.

References

[1] Rosen K, Raanani E, Kogan A, et al. Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: risk factors and management[J]. J Heart Lung Transplant, 2022,41:208-216. doi:10.1016/j.healun.2021.10.016.
[2] Barco S, Mavromanoli AC, Kreitner KF, et al. Preexist-ing chronic thromboembolic pulmonary hypertension in acute pulmonary embolism[J]. Chest, 2023,163:923-932. doi:10.1016/j.chest.2022.11.045.
[3] Durrington C, Hurdman JA, Elliot CA, et al. Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry[J]. Eur Respir J, 2024,63:2300846. doi:10.1183/13993003.00846-2023.
[4] Liley J, Newnham M, Bleda M, et al. Shared and distinct genomics of chronic thromboembolic pulmonary hyperten-sion and pulmonary embolism[J]. Am J Respir Crit Care Med, 2024,209:1477-1485. doi:10.1164/rccm.202307-1236OC.
[5] Valerio L, Mavromanoli AC, Barco S, et al. Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study[J]. Eur Heart J, 2022,43:3387-3398. doi:10.1093/eurheartj/ehac206.
[6] Klok FA, Vágó E, Horváth-Puhó E, et al. Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark[J]. J Thromb Haemost, 2024,22:3562-3571. doi:10.1016/j.jtha.2024.09.006.
[7] Quarck R, Wynants M, Verbeken E, et al. Contribution of inflammation and impaired angiogenesis to the pathobiology of chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2015,46:431-443. doi:10.1183/09031936.00009914.
[8] Manz XD, Szulcek R, Pan X, et al. Epigenetic modification of the von Willebrand factor promoter drives platelet aggregation on the pulmonary endothelium in chronic thromboembolic pulmonary hypertension[J]. Am J Respir Crit Care Med, 2022,205:806-818. doi:10.1164/rccm.202109-2075OC.
[9] Heuts S, Kawczynski MJ, Leus A, et al. The volume-outcome relationship for pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2025,65:2401865. doi:10.1183/13993003.01865-2024.
[10] Delcroix M, Pepke-Zaba J, D′Armini AM, et al. Worldwide CTEPH registry: long-term outcomes with pulmonary endarterectomy, balloon pulmonary angioplasty, and medical therapy[J]. Circulation, 2024,150:1354-1365. doi:10.1161/CIRCULATIONAHA.124.068610.
[11] Jaïs X, Brenot P, Bouvaist H, et al. Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study[J]. Lancet Respir Med, 2022,10:961-971. doi:10.1016/S2213-260000214-4.
[12] Viswanathan G, Kirshner HF, Nazo N, et al. Single-cell analysis reveals distinct immune and smooth muscle cell populations that contribute to chronic thromboem-bolic pulmonary hypertension[J]. Am J Respir Crit Care Med, 2023,207:1358-1375. doi:10.1164/rccm.202203-0441OC.
[13] Miao R, Dong X, Gong J, et al. Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing[J]. Aging (Albany NY), 2021,13:16485-16499. doi:10.18632/aging.203168.
[14] Miao R, Dong X, Gong J, et al. Examining the development of chronic thromboembolic pulmonary hypertension at the single-cell level[J]. Hypertension, 2022,79:562-574. doi:10.1161/HYPERTENSIONAHA.121.18105.
[15] Chen M, Wu Q, Shao N, et al. The significance of CD16⁺ monocytes in the occurrence and development of chronic thromboembolic pulmonary hypertension: insights from single-cell RNA sequencing[J]. Front Immunol, 2024,15:1446710.doi:10.3389/fimmu.2024.1446710.
[16] Eichstaedt CA. Genetically identifying the “Thromboembolic” in chronic thromboembolic pulmonary hypertension[J]. Am J Respir Crit Care Med, 2024,209:1425-1426. doi:10.1164/rccm.202402-0471ED.
[17] Yaoita N, Satoh K, Satoh T, et al. Identification of the novel variants in patients with chronic thromboembolic pulmonary hypertension[J]. J Am Heart Assoc, 2020,9:e015902. doi:10.1161/JAHA.120.015902.
[18] Zhang Y, Zhang M, Yang H, et al. Serum proteome profiling reveals heparanase as a candidate biomarker for chronic thromboembolic pulmonary hypertension[J]. iScience, 2024,27:108930.doi:10.1016/j.isci.2024.108930.
[19] Xu WJ, Wang S, Zhao QH, et al. Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension[J]. Front Immunol, 2024,15:1402250. doi:10.3389/fimmu.2024.1402250.
[20] Nukala SB, Tura-Ceide O, Aldini G, et al. Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension[J]. Sci Rep, 2021,11:5583. doi:10.1038/s41598-021-85004-z.
[21] Swietlik EM, Ghataorhe P, Zalewska KI, et al. Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2021,57:2003201.doi:10.1183/13993003.03201-2020.
[22] Liu J, Chang Z, Zhang Z, et al. Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hyperten-sion[J]. Front Cardiovasc Med, 2022,9:1023282.doi:10.3389/fcvm.2022.1023282.
[23] Carlsen J, Henriksen HH, Marin de Mas I, et al. An explorative metabolomic analysis of the endothelium in pulmonary hypertension[J]. Sci Rep, 2022,12:13284. doi:10.1038/s41598-022-17374-x.
[24] Argelaguet R, Velten B, Arnol D, et al. Multi-omics factor analysis-a framework for unsupervised integration of multi-omics data sets[J]. Mol Syst Biol, 2018,14:e8124. doi:10.15252/msb.20178124.
[25] Baysoy A, Bai Z, Satija R, et al. The technological landscape and applications of single-cell multi-omics[J]. Nat Rev Mol Cell Biol,2023,24:695-713. doi:10.1038/s41580-023-00615-w.