The Functional Molecular Biopsy: Exercise-Induced Transpulmonary Multi-Omic Profiling in Pulmonary Arterial Hypertension
- 1Division of Respiratory Diseases, Department of Medicine, Hospital São Paulo, Federal University of São Paulo (UNIFESP), São Paulo 04024-002, SP, Brazil
- 2Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
Abstract
Pulmonary hypertension (PH) is a disease in which diverse pathogenic drivers converge to promote inflammatory vascular remodeling, ultimately leading to right ventricular (RV) dysfunction and heart failure. Exercise right heart catheterization (RHC) reveals abnormal pulmonary vascular responses early in the disease course and improves diagnosis and risk stratification in PH. Despite major advances in PH research, direct access to the biological processes driving pulmonary vascular remodeling remains limited. Existing clinical assessments predominantly capture the consequences of disease rather than its causes, while tissue-based studies are constrained by limited access to early-stage human samples and the inability to perform serial measurements. This creates a critical need for methodologies capable of interrogating pulmonary vascular biology in vivo and across the disease continuum. We propose that combining exercise RHC with paired transpulmonary omics measurements may provide such an opportunity. The strategy of measuring the change in molecular concentrations across the pulmonary circulation during physiological stress has the potential to function as a dynamic molecular biopsy of the pulmonary vasculature, linking abnormal exercise hemodynamics to the biological pathways that drive disease, although current supporting evidence remains limited to small, heterogeneous proof-of-concept cohorts. In this review, we examine the physiological basis, technical framework, biological insights, and translational implications of this emerging approach for PH.
Related
- Transcriptomic Profiling of Adherent Cells Isolated from Wedged Pulmonary Arterial Blood of Patients with Pulmonary Arterial Hypertension Reveals a Predominantly Myeloid Rather than Endothelial Phenotype
- Machine learning, molecular docking, and experimental validation identify shared molecular signatures between idiopathic pulmonary arterial hypertension and malignant pleural mesothelioma: a retrospective study.
- A Machine Learning Framework for Predicting Functional Status and Estimating Health Care Costs in Pulmonary Arterial Hypertension: Retrospective Cohort Study
- Bile acid dysregulation in pulmonary arterial hypertension: strengthening the liver-lung axis in pulmonary vascular disease
- Intratracheal Administration of Benzbromarone Attenuates Pulmonary Vascular Remodeling and Improves Survival in Rats with Monocrotaline-Induced Pulmonary Hypertension
BibTeX
@article{oliveira2026functional,
title = {{The Functional Molecular Biopsy: Exercise-Induced Transpulmonary Multi-Omic Profiling in Pulmonary Arterial Hypertension}},
author = {Fernanda P. Oliveira and Thais C. F. Menezes and Claudia Mickael and Rudolf K. F. Oliveira},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209130},
url = {https://www.mdpi.com/1422-0067/27/20/9130},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Functional Molecular Biopsy: Exercise-Induced Transpulmonary Multi-Omic Profiling in Pulmonary Arterial Hypertension
AU - Fernanda P. Oliveira
AU - Thais C. F. Menezes
AU - Claudia Mickael
AU - Rudolf K. F. Oliveira
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209130
UR - https://www.mdpi.com/1422-0067/27/20/9130
AB - Pulmonary hypertension (PH) is a disease in which diverse pathogenic drivers converge to promote inflammatory vascular remodeling, ultimately leading to right ventricular (RV) dysfunction and heart failure. Exercise right heart catheterization (RHC) reveals abnormal pulmonary vascular responses early in the disease course and improves diagnosis and risk stratification in PH. Despite major advances in PH research, direct access to the biological processes driving pulmonary vascular remodeling remains limited. Existing clinical assessments predominantly capture the consequences of disease rather than its causes, while tissue-based studies are constrained by limited access to early-stage human samples and the inability to perform serial measurements. This creates a critical need for methodologies capable of interrogating pulmonary vascular biology in vivo and across the disease continuum. We propose that combining exercise RHC with paired transpulmonary omics measurements may provide such an opportunity. The strategy of measuring the change in molecular concentrations across the pulmonary circulation during physiological stress has the potential to function as a dynamic molecular biopsy of the pulmonary vasculature, linking abnormal exercise hemodynamics to the biological pathways that drive disease, although current supporting evidence remains limited to small, heterogeneous proof-of-concept cohorts. In this review, we examine the physiological basis, technical framework, biological insights, and translational implications of this emerging approach for PH.
SN - 1422-0067
ER -