Microfluidic captured patient-derived circulating endothelial cells identify novel targets of pulmonary arterial hypertension Article Swipe
Riajul Wahab
,
Ali Keshavarz
,
Zulfikar Azam
,
Tamanna Islam
,
Md. Mahedi Hasan
,
Xiaojun Zhang
,
Ahmed Alobaida
,
Muhit Rana
,
Jeong Uk Choi
,
Farzana Alam
,
In‐San Kim
,
Youngro Byun
,
Joseph H. McCarty
,
Nils Nickel
,
Sourav Roy
,
Taslim A. Al-Hilal
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.biomaterials.2025.123429
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.biomaterials.2025.123429
Endothelial cell (EC) dysfunction and gene expression abnormalities in pulmonary arterial hypertension (PAH) vary among patients. Existing PAH cell sources, often from lung transplant patients, are influenced by drug treatments and are inadequate for identifying early-stage PAH genes. We propose isolating viable circulating endothelial cells (CECs) from the whole blood of PAH patients to evaluate their potential as surrogates for PAH-ECs and discover novel gene expression profiles relevant to PAH. We developed a microfluidic bioengineering system to directly detect and separate CECs from the blood of PAH patients. Viable CECs were isolated and compared with those from healthy individuals and PAH patients. Differentially expressed genes (DEGs) were identified, and the role of the novel gene PRND in PAH was investigated using in vitro, genomic, and in vivo methods. CEC levels were higher in PAH patients and correlated with disease severity. Transcriptomic analysis revealed 138 DEGs when comparing healthy controls with PAH patients of intermediate severity. These DEGs were associated with PAH-specific markers and angiogenesis. The Doppel (PRND) gene, previously unlinked to PAH, was significantly upregulated in PAH-CECs and PAH-ECs. Overexpression of Doppel in human PAH-ECs matched 13-15 % of DEGs related to hypoxia and endothelial-to-mesenchymal transition (EndMT). Doppel blocking or knockdown in ECs activated the BMPRII/pSMAD1/5 pathway and altered EndMT-related gene levels, while Doppel-knockout mice showed reduced right ventricular systolic pressure in Sugen/Hypoxia PH model. Collectively our findings demonstrate that PAH patient-derived CECs are a promising tool for identifying novel genes involved in PAH pathogenesis.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.biomaterials.2025.123429
- OA Status
- hybrid
- Cited By
- 2
- References
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- Related Works
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- OpenAlex ID
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https://openalex.org/W4410487951Canonical identifier for this work in OpenAlex
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https://doi.org/10.1016/j.biomaterials.2025.123429Digital Object Identifier
- Title
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Microfluidic captured patient-derived circulating endothelial cells identify novel targets of pulmonary arterial hypertensionWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-05-19Full publication date if available
- Authors
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Riajul Wahab, Ali Keshavarz, Zulfikar Azam, Tamanna Islam, Md. Mahedi Hasan, Xiaojun Zhang, Ahmed Alobaida, Muhit Rana, Jeong Uk Choi, Farzana Alam, In‐San Kim, Youngro Byun, Joseph H. McCarty, Nils Nickel, Sourav Roy, Taslim A. Al-HilalList of authors in order
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https://doi.org/10.1016/j.biomaterials.2025.123429Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.biomaterials.2025.123429Direct OA link when available
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Materials science, Microfluidics, Pulmonary hypertension, Biomedical engineering, Cardiology, Nanotechnology, MedicineTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.comparing | 146 |
| abstract_inverted_index.developed | 71 |
| abstract_inverted_index.expressed | 103 |
| abstract_inverted_index.isolating | 40 |
| abstract_inverted_index.knockdown | 200 |
| abstract_inverted_index.patients, | 24 |
| abstract_inverted_index.patients. | 15, 87, 101 |
| abstract_inverted_index.potential | 56 |
| abstract_inverted_index.promising | 235 |
| abstract_inverted_index.pulmonary | 9 |
| abstract_inverted_index.severity. | 139, 154 |
| abstract_inverted_index.associated | 158 |
| abstract_inverted_index.correlated | 136 |
| abstract_inverted_index.expression | 6, 65 |
| abstract_inverted_index.inadequate | 32 |
| abstract_inverted_index.influenced | 26 |
| abstract_inverted_index.previously | 168 |
| abstract_inverted_index.surrogates | 58 |
| abstract_inverted_index.transition | 195 |
| abstract_inverted_index.transplant | 23 |
| abstract_inverted_index.treatments | 29 |
| abstract_inverted_index.Endothelial | 0 |
| abstract_inverted_index.circulating | 42 |
| abstract_inverted_index.demonstrate | 228 |
| abstract_inverted_index.dysfunction | 3 |
| abstract_inverted_index.early-stage | 35 |
| abstract_inverted_index.endothelial | 43 |
| abstract_inverted_index.identified, | 107 |
| abstract_inverted_index.identifying | 34, 238 |
| abstract_inverted_index.individuals | 98 |
| abstract_inverted_index.upregulated | 174 |
| abstract_inverted_index.ventricular | 218 |
| abstract_inverted_index.Collectively | 225 |
| abstract_inverted_index.PAH-specific | 160 |
| abstract_inverted_index.hypertension | 11 |
| abstract_inverted_index.intermediate | 153 |
| abstract_inverted_index.investigated | 119 |
| abstract_inverted_index.microfluidic | 73 |
| abstract_inverted_index.EndMT-related | 209 |
| abstract_inverted_index.Sugen/Hypoxia | 222 |
| abstract_inverted_index.abnormalities | 7 |
| abstract_inverted_index.angiogenesis. | 163 |
| abstract_inverted_index.pathogenesis. | 244 |
| abstract_inverted_index.significantly | 173 |
| abstract_inverted_index.Differentially | 102 |
| abstract_inverted_index.Overexpression | 179 |
| abstract_inverted_index.Transcriptomic | 140 |
| abstract_inverted_index.bioengineering | 74 |
| abstract_inverted_index.BMPRII/pSMAD1/5 | 205 |
| abstract_inverted_index.Doppel-knockout | 213 |
| abstract_inverted_index.patient-derived | 231 |
| abstract_inverted_index.endothelial-to-mesenchymal | 194 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 95 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 16 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/2 |
| sustainable_development_goals[0].score | 0.44999998807907104 |
| sustainable_development_goals[0].display_name | Zero hunger |
| citation_normalized_percentile.value | 0.94857585 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |