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Peer-reviewedCC BYInternational journal of molecular sciences

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

  1. 1Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia
  2. 2Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia

Abstract

Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and immune dysregulation. Myeloid angiogenic cells (MACs) are blood-derived mononuclear cells that acquire endothelial-like features at sites of vascular injury, but their transcriptomic phenotype in the pulmonary vascular compartment is poorly characterized. We isolated adherent cells from blood aspirated from the wedged pulmonary artery of four patients with severe PAH during right heart catheterization. The cells were vWF-positive and ACTA2-negative by immunocytochemistry and co-expressed canonical endothelial (CDH5, PECAM1, ERG, FLT1) and myeloid (PTPRC/CD45, CD14, SPI1, IRF8) transcripts, consistent with MAC-like adherent cultures rather than a conventional endothelial population. Bulk RNA sequencing of these cultures was compared with human pulmonary artery endothelial cells (HPAECs) and HUVECs used as endothelial reference cultures. Relative to both references, PAH MACs showed higher transcript levels of cytokines (IL1A, TNF, IL15, IL10) and matrix metalloproteinases (MMP8/9/12); relative to HPAECs, they showed lower levels of Notch-associated genes (DLL4, HEYL). Protein–protein interaction analysis identified modules centered on complement components, myeloid immune receptors and CC chemokines. Because MACs from non-PAH subjects were not available, these differences describe the phenotype of PAH-derived MACs relative to endothelial reference cells rather than a PAH-specific effect. Adherent cultures obtained from wedged pulmonary arterial blood are therefore dominated by a mononuclear phagocyte transcriptional program, which has direct implications for the design of patient-derived pulmonary vascular cell models.

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BibTeX
@article{boyarskaya2026transcriptomic,
  title = {{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}},
  author = {Nadezhda Boyarskaya and Polina Kuchur and Pavel Docshin and Olga Skortsanu and Daria Smirnova and Natalia Goncharova and Elizaveta Korobchenko and Kirill Lapshin and Olga Moiseeva and Anna Malashicheva},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198799},
  url = {https://europepmc.org/article/PMC/PMC13665573},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - 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
AU  - Nadezhda Boyarskaya
AU  - Polina Kuchur
AU  - Pavel Docshin
AU  - Olga Skortsanu
AU  - Daria Smirnova
AU  - Natalia Goncharova
AU  - Elizaveta Korobchenko
AU  - Kirill Lapshin
AU  - Olga Moiseeva
AU  - Anna Malashicheva
PY  - 2026
DA  - 2026/10/01
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198799
UR  - https://europepmc.org/article/PMC/PMC13665573
AB  - Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling and immune dysregulation. Myeloid angiogenic cells (MACs) are blood-derived mononuclear cells that acquire endothelial-like features at sites of vascular injury, but their transcriptomic phenotype in the pulmonary vascular compartment is poorly characterized. We isolated adherent cells from blood aspirated from the wedged pulmonary artery of four patients with severe PAH during right heart catheterization. The cells were vWF-positive and ACTA2-negative by immunocytochemistry and co-expressed canonical endothelial (CDH5, PECAM1, ERG, FLT1) and myeloid (PTPRC/CD45, CD14, SPI1, IRF8) transcripts, consistent with MAC-like adherent cultures rather than a conventional endothelial population. Bulk RNA sequencing of these cultures was compared with human pulmonary artery endothelial cells (HPAECs) and HUVECs used as endothelial reference cultures. Relative to both references, PAH MACs showed higher transcript levels of cytokines (IL1A, TNF, IL15, IL10) and matrix metalloproteinases (MMP8/9/12); relative to HPAECs, they showed lower levels of Notch-associated genes (DLL4, HEYL). Protein–protein interaction analysis identified modules centered on complement components, myeloid immune receptors and CC chemokines. Because MACs from non-PAH subjects were not available, these differences describe the phenotype of PAH-derived MACs relative to endothelial reference cells rather than a PAH-specific effect. Adherent cultures obtained from wedged pulmonary arterial blood are therefore dominated by a mononuclear phagocyte transcriptional program, which has direct implications for the design of patient-derived pulmonary vascular cell models.
SN  - 1422-0067
ER  -