Large-scale proteomics identifies circulating markers of pulmonary pressure and pulmonary hypertension risk

Abstract

Pulmonary hypertension, defined by elevated pressure in the pulmonary circulation, is morbid and diagnosing is challenging as no early-stage blood markers are currently available. Here we show that large-scale proteomic profiling across several independent observational cohorts identifies 22 proteins associated with echocardiography-derived pulmonary artery systolic pressure, several of which are independently associated with invasive measures of pulmonary vascular disease, structural remodeling of the pulmonary vasculature, and subsequent risk of pulmonary hypertension. Genetic analyses support a potential causal role for NOTCH3 and identify a common splice-regulating genetic variant that may modify susceptibility to pulmonary vascular stressors. Protein-based clustering further reveals two distinct biological subtypes associated with increased risk of pulmonary hypertension. Together, these findings identify candidate biomarkers of pulmonary hypertension, implicate pulmonary vascular remodeling in early-stage disease with a potential causal role for NOTCH3, and discover and validate two distinct endotypes of pulmonary hypertension risk in the community.

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Cite

BibTeX RIS

BibTeX

@article{giugni2026largescale,
  title = {{Large-scale proteomics identifies circulating markers of pulmonary pressure and pulmonary hypertension risk}},
  author = {Fernando R. Giugni and Mario Santos and Yimin Yang and Victoria Lamberson and Brian Claggett and Ron Hoogeveen and Christie Ballantyne and David Systrom and Aaron Waxman and Leo Buckley and Bing Yu and Raúl San José Estépar and Sheila M. Hegde and Amil M. Shah},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78432-w},
  url = {https://www.nature.com/articles/s41467-026-78432-w},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Large-scale proteomics identifies circulating markers of pulmonary pressure and pulmonary hypertension risk
AU  - Fernando R. Giugni
AU  - Mario Santos
AU  - Yimin Yang
AU  - Victoria Lamberson
AU  - Brian Claggett
AU  - Ron Hoogeveen
AU  - Christie Ballantyne
AU  - David Systrom
AU  - Aaron Waxman
AU  - Leo Buckley
AU  - Bing Yu
AU  - Raúl San José Estépar
AU  - Sheila M. Hegde
AU  - Amil M. Shah
PY  - 2026
DA  - 2026/10/05
JO  - Nature Communications
DO  - 10.1038/s41467-026-78432-w
UR  - https://www.nature.com/articles/s41467-026-78432-w
AB  - Pulmonary hypertension, defined by elevated pressure in the pulmonary circulation, is morbid and diagnosing is challenging as no early-stage blood markers are currently available. Here we show that large-scale proteomic profiling across several independent observational cohorts identifies 22 proteins associated with echocardiography-derived pulmonary artery systolic pressure, several of which are independently associated with invasive measures of pulmonary vascular disease, structural remodeling of the pulmonary vasculature, and subsequent risk of pulmonary hypertension. Genetic analyses support a potential causal role for NOTCH3 and identify a common splice-regulating genetic variant that may modify susceptibility to pulmonary vascular stressors. Protein-based clustering further reveals two distinct biological subtypes associated with increased risk of pulmonary hypertension. Together, these findings identify candidate biomarkers of pulmonary hypertension, implicate pulmonary vascular remodeling in early-stage disease with a potential causal role for NOTCH3, and discover and validate two distinct endotypes of pulmonary hypertension risk in the community.
SN  - 2041-1723
ER  -

Abstract

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