{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:51:50Z","timestamp":1791597110920,"version":"4.3.4"},"reference-count":32,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["26-15-00311"],"award-info":[{"award-number":["26-15-00311"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2013protein 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.<\/jats:p>","DOI":"10.3390\/ijms27198799","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:25:44Z","timestamp":1790850344000},"page":"8799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-770X","authenticated-orcid":false,"given":"Nadezhda","family":"Boyarskaya","sequence":"first","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"},{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-577X","authenticated-orcid":false,"given":"Polina","family":"Kuchur","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Pavel","family":"Docshin","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"},{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5388-8474","authenticated-orcid":false,"given":"Olga","family":"Skortsanu","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Daria","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Natalia","family":"Goncharova","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Elizaveta","family":"Korobchenko","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Kirill","family":"Lapshin","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Olga","family":"Moiseeva","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, 2 Akkuratova St., 197341 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-2913","authenticated-orcid":false,"given":"Anna","family":"Malashicheva","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1161\/HYPERTENSIONAHA.122.18261","article-title":"Evolving Concepts in Endothelial Pathobiology of Pulmonary Arterial Hypertension","volume":"79","author":"Cober","year":"2022","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S2213-2600(23)00264-3","article-title":"Treatment of pulmonary arterial hypertension: Recent progress and a look to the future","volume":"11","author":"Humbert","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2003957","DOI":"10.1183\/13993003.03957-2020","article-title":"Endothelial cells in the pathogenesis of pulmonary arterial hypertension","volume":"58","author":"Evans","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Awad, K.S., Wang, S., Dougherty, E.J., Keshavarz, A., Demirkale, C.Y., Yu, Z.X., Miller, L., Elinoff, J.M., and Danner, R.L. (2024). BMPR2 Loss Activates AKT by Disrupting DLL4\/NOTCH1 and PPARgamma Signaling in Pulmonary Arterial Hypertension. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105403"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1901313","DOI":"10.1183\/13993003.01313-2019","article-title":"Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: Considerations for use in pulmonary vascular disease","volume":"55","author":"Ventetuolo","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.2147\/IJGM.S295463","article-title":"Treating Inflammation Associated with Pulmonary Hypertension: An Overview of the Literature","volume":"15","author":"Yoo","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1164\/rccm.202102-0446OC","article-title":"Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension","volume":"206","author":"Taylor","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/bph.14826","article-title":"The role of chemokines and chemokine receptors in pulmonary arterial hypertension","volume":"178","author":"Mamazhakypov","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s10020-024-00963-z","article-title":"Assessing personalized molecular portraits underlying endothelial-to-mesenchymal transition within pulmonary arterial hypertension","volume":"30","author":"Wu","year":"2024","journal-title":"Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22534","DOI":"10.1038\/s41598-023-48077-6","article-title":"Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension","volume":"13","author":"Singh","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1161\/CIRCULATIONAHA.120.052318","article-title":"Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung","volume":"144","author":"Schupp","year":"2021","journal-title":"Circulation"},{"key":"ref_12","first-page":"e58353","article-title":"Harvest of Endothelial Cells from the Balloon Tips of Swan-Ganz Catheters after Right Heart Catheterization","volume":"143","author":"Passineau","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41569-022-00739-0","article-title":"Mechanisms and consequences of endothelial cell senescence","volume":"20","author":"Bloom","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aulak, K.S., Mavarakis, L., Tian, L., Paul, D., Comhair, S.A., Dweik, R.A., and Tonelli, A.R. (2024). Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0312535"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2353\/ajpath.2008.070705","article-title":"Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension","volume":"172","author":"Asosingh","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1164\/rccm.200810-1662OC","article-title":"Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension","volume":"180","author":"Toshner","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","first-page":"58","article-title":"Endothelial Cells of the Pulmonary Artery in Vitro: How to Overcome the Deficiency of a Model Object in the Study of Pulmonary Arterial Hypertension?","volume":"14","author":"Boyarskaya","year":"2025","journal-title":"Complex Issues Cardiovasc. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/nm.2021","article-title":"Notch3 signaling promotes the development of pulmonary arterial hypertension","volume":"15","author":"Li","year":"2009","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106662","DOI":"10.1016\/j.isci.2023.106662","article-title":"Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells","volume":"26","author":"Ramadhiani","year":"2023","journal-title":"iScience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1172\/JCI107470","article-title":"Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria","volume":"52","author":"Jaffe","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_21","unstructured":"Andrews, S. (2026, August 30). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11.14.1","DOI":"10.1002\/0471250953.bi1114s51","article-title":"Mapping RNA-seq Reads with STAR","volume":"51","author":"Dobin","year":"2015","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_27","unstructured":"Allaire, J. (2024). RStudio: Integrated Development Environment for R, Posit Software, PBC."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_30","unstructured":"Kolde, R. (2026, August 30). pheatmap: Pretty Heatmaps. R Package Version 1.0.13. Available online: https:\/\/CRAN.R-project.org\/package=pheatmap."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"27","author":"Ogata","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:43:37Z","timestamp":1791596617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":32,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198799"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198799","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}