The N‑Glycoproteomic Landscape of the Lung in Monocrotaline-Induced Pulmonary Arterial Hypertension

  • ACS Omega. 2026 Jun 3;11(23):34404-34419. doi: 10.1021/acsomega.6c02324.
Guili Lian  1  2  3  4  5 ,  Mohammad Ismail Hajary Sagor  1  2  3  4  5 ,  Kexin Cai  1  2  3  4  5 ,  Zhihai Chen  1  2  3  4  5 ,  Changsheng Xu  1  2  3  4  5 ,  Huajun Wang  1  2  3  4  5 ,  Wei Zhuang  2  6  7 ,  Li Luo  1  2  3  4  5 ,  Liangdi Xie  1  2  3  4  5
Affiliations
  • 1. Department of Geriatrics, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 2. Fujian Hypertension Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 3. Department of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
  • 4. Clinical Research Center for Geriatric Hypertension Disease of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 5. Branch of National Clinical Research Center for Aging and Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
  • 6. Department of Cardiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
  • 7. Department of Cardiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
PMID: 42326732 DOI: 10.1021/acsomega.6c02324
Abstract

Protein N-glycosylation plays critical roles in controlling cell function, yet its specific contributions to pulmonary arterial hypertension (PAH) remain poorly understood. Here, we performed an integrated proteomic and site-specific N-glycoproteomic analysis of lung tissues from a monocrotaline-induced PAH rat model. Using quantitative LC-MS/MS with glycoprotein enrichment, we identified 7,048 proteins in the proteome, including 1,302 differentially expressed proteins and 1,918 N-glycosylation sites across 764 glycoproteins in the N-glycoproteome. 320 glycosylation sites (from 260 glycoproteins) showed significant dysregulation. Glycoproteomic motif analysis confirmed the canonical N-X-S/T sequon, with enriched localization in plasma membrane and extracellular proteins. Bioinformatics revealed ribosome-related pathways were significantly downregulated, whereas lysosomal pathways were upregulated. Key N-glycoproteomic alterations involved Integrin binding, ECM-receptor interaction, and Ferroptosis. Integrated multiomics analysis of 7,136 proteome and 2,897 N-glycoproteome proteins identified 805 overlapping candidates, of which 387 exhibited concordant upregulation in lysosome, TGF-β signaling, and mineral absorption pathways. We confirmed that VCAM1 and AMBP were increased in the lungs of PAH rats by Western blot and immunofluorescence. Our study provides the first system-wide view of the N-glycoproteomic landscape of the lung in monocrotaline-induced PAH rats, revealing the involvement of N-glycosylation in ECM dysfunction, adhesion pathways, and lysosomal dysregulation, and suggests novel glycoprotein-centered targets for therapeutic intervention.

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