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December 18, 2023Scientific ReportsOpen Access

Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension

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Why the study?

Data from living patients were lacking to inform whether differential gene expression of pulmonary artery endothelial cells can discern disease subtypes, progression, and pathogenesis.

Does differential gene expression of pulmonary artery endothelial cells isolated from right heart catheter balloons discern disease subtypes and pathogenesis in patients with pulmonary hypertension?

Comparison

PAH vs controls and other forms of pulmonary hypertension

Key result

Pulmonary artery endothelial cells isolated from living patients with pulmonary arterial hypertension demonstrated 667 differentially expressed genes compared to controls.

Authors

NSNavneet SinghCECarsten EickhoffAGAugusto García-Agúndez

Discussion

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Overview

Supports novel endothelial cell sampling from PAH patients during catheterization; leaves open subtype discrimination and therapeutic implications.

Study Design

Type

Observational (n=49)

Multicenter

No

Structured PICO

Does differential gene expression of pulmonary artery endothelial cells isolated from right heart catheter balloons discern disease subtypes and pathogenesis in patients with pulmonary hypertension?

P
Population
49 subjects (yielding 54 right heart catheter balloon tips) undergoing right heart catheterization, median age 63 years, 69% female. Included 20 with Group 1 PAH, 18 with Group 2 PH, 8 with Group 3 PH, 1 with Group 4 PH, 4 with Group 5 PH, and 3 controls without PH.
I
Intervention
Isolation, propagation, and bulk RNA sequencing of pulmonary artery endothelial cells (PAECs) from right heart catheter balloon tips, along with functional assays for anoikis resistance.
C
Comparator
PAECs from control subjects without pulmonary hypertension and subjects with other forms of pulmonary hypertension (Groups 2-5).
O
Outcome
Differential gene expression (transcriptional signatures) of PAECs between PAH subjects and controls.surrogate

Main Result

p-value: p=<0.05

Pulmonary artery endothelial cells harvested from routine right heart catheterization balloons in living PAH patients exhibit distinct transcriptional profiles and anoikis resistance, providing a novel 'cell biopsy' method for studying pulmonary vascular disease.

Limitations

  • Inability to definitively prove that cultured cells are exclusively from the pulmonary artery.
  • Potential for the genetic signature of endothelial cells to change with serial passaging.
  • Imbalance in clinical groups, including the use of controls who underwent catheterization for clinical evaluation rather than being pure healthy controls.
  • Unknown genetic mutation status for most of the patients who provided samples.
  • Low clinical event rate during follow-up, leaving the study underpowered to assess associations between transcriptional signatures and disease outcomes.
  • Observations need to be confirmed and developed beyond the transcript level.
  • It is not possible to definitively prove that cultured cells are from the pulmonary artery.
  • Potential for phenotypic drift with serial passaging.

Cite This Study

Singh et al. (2023) conducted an observational in Pulmonary hypertension (n=49). Pulmonary artery endothelial cell (PAEC) isolation via right heart catheterization vs. Subjects without pulmonary hypertension (controls) was evaluated on Differential gene expression in PAECs (p=<0.05). Pulmonary artery endothelial cells isolated from living patients with pulmonary arterial hypertension demonstrated 667 differentially expressed genes compared to controls.

synapsesocial.com/papers/6a1bfbf90a1f7575939d4e83https://doi.org/10.1038/s41598-023-48077-6
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