Cited by 48MicroRNA in disease regulationAngiogenesis and VEGF in CancerTelomeres, Telomerase, and Senescence

MicroRNA profiling reveals distinct profiles for tissue-derived and cultured endothelial cells

Open access
Kuosmanen, Suvi M., Kansanen, Emilia, Sihvola, Virve, Levonen, Anna-Liisa·2017·Scientific Reports

Abstract

Endothelial plasticity enables the cells to switch their phenotype according to the surrounding vascular microenvironment. MicroRNAs (miRNAs) are small noncoding RNAs that control endothelial plasticity. The objective of this study was to investigate the differences in miRNA profiles of tissue-derived cells and cultured endothelial cells. To this end, miRNA expression was profiled from freshly isolated tissue-derived human vascular endothelial cells and endothelial cells cultured until cellular senescence using miRNA sequencing. In addition, the data was searched for putative novel endothelial miRNAs and miRNA isoforms. The data analysis revealed a striking change in endothelial miRNA profile as the cells adapted from tissue to cell culture environment and the overall miRNA expression decreased significantly in cultured compared to tissue-derived endothelial cells. In addition to changes in mechanosensitive miRNA expression, alterations in senescence-associated and endothelial-to-mesenchymal-transition-associated miRNAs were observed in aging cells. Collectively, the data illustrates the adaptability of endothelial cell miRNA expression that mirrors prevailing cellular environment.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-017-11487-4

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Ex vivo conditions are known to sometimes dramatically alter miRNA expression patterns, as seen for passaged endothelial cells.

    “Ex vivo conditions are known to sometimes dramatically alter miRNA expression patterns, as seen for passaged endothelial cells [24].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–97 (2004). · DOI
  2. Kozomara, A. & Griffiths-Jones, S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42, D68–D73 (2014). · DOI · Paper page
  3. Mullokandov, G. et al. High-throughput assessment of microRNA activity and function using microRNA sensor and decoy libraries. Nat. Methods 9, 840–846 (2012). · DOI · Paper page
  4. Kent, O. A., McCall, M. N., Cornish, T. C. & Halushka, M. K. Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res. 42, 7528–38 (2014). · DOI · Paper page
  5. Aman, J. & Weijers, E. M. van Nieuw Amerongen, G. P., Malik, A. B. & van Hinsbergh, V. W. M. Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities. Am. J. Physiol. - Lung Cell. Mol. Physiol. 311, L453–L466 (2016). · DOI
  6. Potente, M. & Carmeliet, P. The Link Between Angiogenesis and Endothelial Metabolism. Annu. Rev. Physiol. 79, annurev-physiol-021115-105134 (2017). · DOI
  7. Guo, Y., Xu, A. & Wang, Y. SIRT1 in Endothelial Cells as a Novel Target for the Prevention of Early Vascular Aging. J. Cardiovasc. Pharmacol. 67, 465–473 (2016). · DOI
  8. Bochenek, M. L., Schütz, E. & Schüfer, K. Endothelial cell senescence and thrombosis: Ageing clots. Thromb. Res. 147, 36–45 (2016). · DOI · Paper page
  9. Prattichizzo, F. et al. Endothelial Cell Senescence and Inflammaging: MicroRNAs as Biomarkers and Innovative Therapeutic Tools. Curr. Drug Targets 17, 388–97 (2016). · DOI
  10. Vestweber, D. VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler. Thromb. Vasc. Biol. 28, 223–32 (2008). · DOI
  11. Wang, S. et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev. Cell 15, 261–71 (2008). · DOI
  12. Miki, K. et al. Efficient Detection and Purification of Cell Populations Using Synthetic MicroRNA Switches. Cell Stem Cell 16, 699–711 (2015). · DOI
  13. Boon, R. A., Hergenreider, E. & Dimmeler, S. Atheroprotective mechanisms of shear stress-regulated microRNAs. Thromb. Haemost. 108, 616–620 (2012). · DOI · Paper page
  14. Miano, J. M. & Long, X. The short and long of noncoding sequences in the control of vascular cell phenotypes. Cell. Mol. Life Sci. 72, 3457–88 (2015). · DOI
  15. Neth, P., Nazari-Jahantigh, M., Schober, A. & Weber, C. MicroRNAs in flow-dependent vascular remodelling. Cardiovasc. Res. 99, 294–303 (2013). · DOI
  16. Santoro, M. M. & Nicoli, S. MiRNAs in endothelial cell signaling: The endomiRNAs. Exp. Cell Res. 319, 1324–1330 (2013). · DOI
  17. Yamakuchi, M. MicroRNAs in Vascular Biology. Int. J. Vasc. Med. 2012, 1–13 (2012). · DOI
  18. Chen, X., Zheng, S. & Wu, H. Role of microRNAs in endothelial function. Chin. Med. J. (Engl). 126, 1779–86 (2013). · DOI
  19. Chamorro-Jorganes, A., Araldi, E. & Suárez, Y. MicroRNAs as pharmacological targets in endothelial cell function and dysfunction. Pharmacol. Res. 75, 15–27 (2013). · DOI
  20. Kumar, S., Kim, C. W., Simmons, R. D. & Jo, H. Role of Flow-Sensitive microRNAs in Endothelial Dysfunction and Atherosclerosis: Mechanosensitive Athero-miRs. Arterioscler. Thromb. Vasc. Biol. 34, 2206–2216 (2014). · DOI
  21. Hergenreider, E. et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat. Cell Biol. 14, 249–56 (2012). · DOI
  22. Marin, T. et al. Mechanosensitive microRNAs—role in endothelial responses to shear stress and redox state. Free Radic. Biol. Med. 64, 61–68 (2013). · DOI
  23. Wang, K.-C. K.-C. et al. Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc. Natl. Acad. Sci. U. S. A. 107, 3234–9 (2010). · DOI
  24. Zhou, J., Li, Y.-S. & Chien, S. Shear Stress-Initiated Signaling and Its Regulation of Endothelial Function. Arterioscler. Thromb. Vasc. Biol. 34, 2191–2198 (2014). · DOI
  25. Alexy, T., James, A. M. & Searles, C. D. Shear sensitive microRNAs and atherosclerosis. Biorheology 51, 147–58 (2014). · DOI
  26. Xu, D. & Tahara, H. The role of exosomes and microRNAs in senescence and aging. Adv. Drug Deliv. Rev. 65, 368–375 (2013). · DOI
  27. Gorospe, M. & Abdelmohsen, K. MicroRegulators come of age in senescence. Trends Genet. 27, 233–241 (2011). · DOI
  28. Luo, K. Signaling Cross Talk between TGF-β/Smad and Other Signaling Pathways. Cold Spring Harb. Perspect. Biol. 9, a022137 (2017). · DOI
  29. Xiao, L. & Dudley, A. C. Fine-tuning vascular fate during endothelial-mesenchymal transition. J. Pathol. 241, 25–35 (2017). · DOI
  30. Krenning, G., Barauna, V. G., Krieger, J. E., Harmsen, M. C. & Moonen, J.-R. A. J. Endothelial Plasticity: Shifting Phenotypes through Force Feedback. Stem Cells Int. 2016, 9762959 (2016). · DOI
  31. Piera-Velazquez, S., Mendoza, F. & Jimenez, S. Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases. J. Clin. Med. 5, 45 (2016). · DOI
  32. Kumarswamy, R. et al. Transforming Growth Factor–Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21. Arterioscler. Thromb. Vasc. Biol. 32, 361–369 (2012). · DOI
  33. Bao, M.-H. et al. Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells. Int. J. Mol. Sci. 14, 23086–102 (2013). · DOI
  34. Katsura, A. et al. MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β. Genes to Cells 21, 99–116 (2016). · DOI
  35. Kanasaki, K. et al. Linagliptin-Mediated DPP-4 Inhibition Ameliorates Kidney Fibrosis in Streptozotocin-Induced Diabetic Mice by Inhibiting Endothelial-to-Mesenchymal Transition in a Therapeutic Regimen. Diabetes 63, 2120–2131 (2014). · DOI
  36. ENCODE Project, C. et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012). · DOI · Paper page
  37. Kellis, M. et al. Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. 111, 6131–6138 (2014). · DOI
  38. Zhang, Y. et al. DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data. Nucleic Acids Res. 44, W166–W175 (2016). · DOI
  39. Jaffe, E. A., Nachman, R. L., Becker, C. G. & Minick, C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J. Clin. Invest. 52, 2745–56 (1973). · DOI
  40. Siow, R. C. M. Methods in molecular biology (Clifton, N.J.) 806, 265–274 (2012). · DOI
  41. Conway, E. M. & Carmeliet, P. The diversity of endothelial cells: a challenge for therapeutic angiogenesis. Genome Biol. 5, 207 (2004). · DOI
  42. Chi, J.-T. et al. Endothelial cell diversity revealed by global expression profiling. Proc. Natl. Acad. Sci. 100, 10623–10628 (2003). · DOI
  43. McCall, M. N. et al. MicroRNA profiling of diverse endothelial cell types. BMC Med. Genomics 4, 78 (2011). · DOI
  44. Furchgott, R. F. & Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373–6 (1980). · DOI · Paper page
  45. Poliseno, L. et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108, 3068–3071 (2006). · DOI
  46. Heusschen, R., van Gink, M., Griffioen, A. W. & Thijssen, V. L. MicroRNAs in the tumor endothelium: Novel controls on the angioregulatory switchboard. Biochim. Biophys. Acta - Rev. Cancer 1805, 87–96 (2010). · DOI
  47. Das, S. & Halushka, M. K. Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc. Pathol. 24, 199–206 (2015). · DOI
  48. Climent, M. et al. TGF Triggers miR-143/145 Transfer From Smooth Muscle Cells to Endothelial Cells, Thereby Modulating Vessel Stabilization. Circ. Res. 116, 1753–1764 (2015). · DOI
  49. Dejana, E., Hirschi, K. K. & Simons, M. The molecular basis of endothelial cell plasticity. Nat. Commun. 8, 14361 (2017). · DOI
  50. Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519–60 (1995). · DOI · Paper page
  51. Huveneers, S., Daemen, M. J. A. P. & Hordijk, P. L. Between Rho(k) and a Hard Place: The Relation Between Vessel Wall Stiffness, Endothelial Contractility, and Cardiovascular Disease. Circ. Res. 116, 895–908 (2015). · DOI
  52. Nelson, G. et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11, 345–9 (2012). · DOI · Paper page
  53. Olivieri, F. et al. MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res. Rev. 12, 1056–68 (2013). · DOI
  54. Telonis, A. G., Loher, P., Jing, Y., Londin, E. & Rigoutsos, I. Beyond the one-locus-one-miRNA paradigm: microRNA isoforms enable deeper insights into breast cancer heterogeneity. Nucleic Acids Res. 43, 9158–75 (2015). · DOI
  55. Loher, P., Londin, E. R. & Rigoutsos, I. IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies. Oncotarget 5, 8790–802 (2014). · DOI · Paper page
  56. Karali, M. et al. High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs. Nucleic Acids Res. 44, 1525–1540 (2016). · DOI
  57. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–9 (2012). · DOI · Paper page
  58. Wu, Y., Wei, B., Liu, H., Li, T. & Rayner, S. MiRPara: a SVM-based software tool for prediction of most probable microRNA coding regions in genome scale sequences. BMC Bioinformatics 12, 107 (2011). · DOI
  59. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–40 (2010). · DOI · Paper page
  60. McCarthy, D. J., Chen, Y. & Smyth, G. K. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288–4297 (2012). · DOI · Paper page
  61. Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–10 (2002). · DOI · Paper page

Cited by

Sorted by citations

Authors
Kuosmanen, S. M., Kansanen, E., Sihvola, V., & Levonen, A.-L.
Affiliations
University of Eastern Finland (FI)
Corresponding author
Levonen, Anna-Liisa
Venue
Scientific Reports
Published
2017-09-08
Volume
7
Issue
1
Pages
10943-10943
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2753544039
Cited by
48
References
6
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 1
FWCI
1.76
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by)
Funders
Academy of Finland
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords
miRNA expression profiling, endothelial plasticity, cultured endothelial cells, cellular senescence, endothelial-to-mesenchymal transition, novel miRNAs, miRNA isoforms, vascular microenvironment
MeSH terms
Humans, Cellular Senescence, Gene Expression Profiling, MicroRNAs, Mechanotransduction, Cellular, Transcriptome, Human Umbilical Vein Endothelial Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review