Key result
PAH therapy concordant with individualized interactome topology is linked to a ~628 pg/mL BNP reduction.
Why the study?
The study tested whether transcriptomic data from pulmonary artery endothelial cell biopsies collected during right heart catheterization could build individualized protein-protein interactomes and inform treatment response.
Does concordance between prescribed PAH pharmacotherapy and individualized interactome topology improve clinical metrics in patients with PAH?
Observational (n=28)
Blinded
No
Does concordance between prescribed PAH pharmacotherapy and individualized interactome topology improve clinical metrics in patients with PAH?
Effect estimate: β -627.6 pg/mL (95% CI -986.4, -268.8)
p-value: p=0.003
Integration of point-of-care transcriptomics to build individualized interactomes may predict therapeutic response and improve clinically relevant endpoints in pulmonary arterial hypertension.
May inform individualized PAH prescribing; hypothesis-generating observational data requiring prospective validation.
clinical trial design to test whether transcriptomic data from pulmonary artery endothelial cell biopsies collected during right heart catheterization could be used to build individualized protein-protein interactomes and inform treatment response. Twenty-five PAH participants (56 [range: 30-84] yr; 91% female; 81%, white) and three controls contributed 32 and three cell biopsy specimens, respectively. Patient-specific interactomes varied widely in topology and complexity. All 32 individualized PAH interactomes were enriched significantly with key PAH endophenotypes genes such as hypoxia, oxidant stress, and apoptosis. Concordance between the molecular targets of a prescribed PAH pharmacotherapy class and the corresponding individualized interactome topology was associated with improvement in multiple PAH metrics, including a reduction in brain natriuretic peptide levels at 6 months (β -627.6 pg/mL, [95% CI -986.4, -268.8]; p = 0.003) and a decrease from high to intermediate REVEAL 2.0 Risk scores at 6 months (β -1.3 units, [95% CI -2.6, -0.04]; p=0.043) that persisted at 12 months (β -1.7, [95% CI -3.4, -0.1]; p=0.059). Integration of transcriptomics acquired at point-of-care with network medicine may individualize treatment selection and improve clinically relevant endpoints in PAH.
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Wang et al. (2025) conducted an observational in Pulmonary arterial hypertension (n=28). Target-interactome alignment of prescribed PAH therapies vs. Non-alignment or inactive comparators was evaluated on Reduction in brain natriuretic peptide (BNP) levels at 6 months (β -627.6 pg/mL, 95% CI -986.4, -268.8, p=0.003). Concordance between the molecular targets of prescribed pulmonary arterial hypertension therapies and individualized interactome topology reduced brain natriuretic peptide levels at 6 months (β -627.6 pg/mL).
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