Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress
Background: Endothelial cell (EC) heterogeneity is an emerging area of research in EC biology. Vein, artery, and microvascular ECs have been shown to have heterogeneity in gene expression and function, termed “vascular-type” heterogeneity in this report. In addition to this innate heterogeneity, we...
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Elsevier
2025-05-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925002183 |
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| author | Allaura A. Cox Christopher James Ng |
| author_facet | Allaura A. Cox Christopher James Ng |
| author_sort | Allaura A. Cox |
| collection | DOAJ |
| description | Background: Endothelial cell (EC) heterogeneity is an emerging area of research in EC biology. Vein, artery, and microvascular ECs have been shown to have heterogeneity in gene expression and function, termed “vascular-type” heterogeneity in this report. In addition to this innate heterogeneity, we hypothesized that different vascular-type ECs would also demonstrate heterogeneity in their response to shear stress. Objectives: We interrogated whether vascular-type ECs would demonstrate variations in transcriptional expression patterns under shear stress. Methods: Human umbilical vein ECs, human pulmonary arterial ECs, and human microvascular ECs were commercially purchased and subjected to 0, 1, 4, and 10 dynes/cm2 of laminar shear stress. After shear stress exposure, cellular alignment was analyzed, and RNA was extracted and evaluated via bulk RNA sequencing. Results: All ECs demonstrated significant changes in alignment under shear stress. Shear stress significantly affected the transcriptomes of ECs, resulting in differential expression of genes and pathways. While several genes were differentially expressed by all 3 vascular EC types (44.2%), most differentially expressed genes were limited to 1 or 2 of the vascular types. Hemostatic and thrombotic genes were found to have differential expression patterns under conditions of shear stress, and von Willebrand factor demonstrated a pattern of vascular-type heterogeneity in response to shear stress. Conclusion: Shear stress causes changes in cellular alignment and transcriptional patterns in ECs that are dependent upon underlying vascular type. Therefore, endothelial vascular-type heterogeneity can regulate response to shear stress, especially in hemostatic and thrombotic gene expression. |
| format | Article |
| id | doaj-art-ba077ee8d4de461d97b5eb93ff61783d |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-ba077ee8d4de461d97b5eb93ff61783d2025-08-20T03:38:19ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-05-019410289410.1016/j.rpth.2025.102894Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stressAllaura A. Cox0Christopher James Ng1Department of Pediatrics, University of Colorado–Anschutz Medical Campus, Aurora, Colorado, USACorrespondence Christopher James Ng, Department of Pediatrics, University of Colorado–Anschutz Medical Campus, 12800 East 19th Ave RC1-North, Aurora, CO 80045-2559, USA.; Department of Pediatrics, University of Colorado–Anschutz Medical Campus, Aurora, Colorado, USABackground: Endothelial cell (EC) heterogeneity is an emerging area of research in EC biology. Vein, artery, and microvascular ECs have been shown to have heterogeneity in gene expression and function, termed “vascular-type” heterogeneity in this report. In addition to this innate heterogeneity, we hypothesized that different vascular-type ECs would also demonstrate heterogeneity in their response to shear stress. Objectives: We interrogated whether vascular-type ECs would demonstrate variations in transcriptional expression patterns under shear stress. Methods: Human umbilical vein ECs, human pulmonary arterial ECs, and human microvascular ECs were commercially purchased and subjected to 0, 1, 4, and 10 dynes/cm2 of laminar shear stress. After shear stress exposure, cellular alignment was analyzed, and RNA was extracted and evaluated via bulk RNA sequencing. Results: All ECs demonstrated significant changes in alignment under shear stress. Shear stress significantly affected the transcriptomes of ECs, resulting in differential expression of genes and pathways. While several genes were differentially expressed by all 3 vascular EC types (44.2%), most differentially expressed genes were limited to 1 or 2 of the vascular types. Hemostatic and thrombotic genes were found to have differential expression patterns under conditions of shear stress, and von Willebrand factor demonstrated a pattern of vascular-type heterogeneity in response to shear stress. Conclusion: Shear stress causes changes in cellular alignment and transcriptional patterns in ECs that are dependent upon underlying vascular type. Therefore, endothelial vascular-type heterogeneity can regulate response to shear stress, especially in hemostatic and thrombotic gene expression.http://www.sciencedirect.com/science/article/pii/S2475037925002183endothelial cellsRNAsequence analysisvon Willebrand factor |
| spellingShingle | Allaura A. Cox Christopher James Ng Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress Research and Practice in Thrombosis and Haemostasis endothelial cells RNA sequence analysis von Willebrand factor |
| title | Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| title_full | Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| title_fullStr | Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| title_full_unstemmed | Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| title_short | Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| title_sort | vascular type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress |
| topic | endothelial cells RNA sequence analysis von Willebrand factor |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925002183 |
| work_keys_str_mv | AT allauraacox vasculartypeheterogeneityisassociatedwithdifferentialgeneexpressionprofilesofendothelialcellsundershearstress AT christopherjamesng vasculartypeheterogeneityisassociatedwithdifferentialgeneexpressionprofilesofendothelialcellsundershearstress |