Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.
<p><em><strong>Aims</strong></em></p> Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell r...
| Egile Nagusiak: | , , , , , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
Oxford University Press
2013
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| _version_ | 1826266476407947264 |
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| author | Douglas, G Van Kampen, E Hale, A McNeill, E Patel, J Crabtree, M Ali, Z Hoerr, R Alp, N Channon, K |
| author_facet | Douglas, G Van Kampen, E Hale, A McNeill, E Patel, J Crabtree, M Ali, Z Hoerr, R Alp, N Channon, K |
| author_sort | Douglas, G |
| collection | OXFORD |
| description | <p><em><strong>Aims</strong></em></p> Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. <p><em><strong>Methods and results</strong></em></p> Endothelial cell repopulation was assessed en face in stented arteries in ApoE<sup>−/−</sup> mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm<sup>2</sup>, <em>P</em> = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm<sup>2</sup>, <em>P</em> = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE<sup>−/−</sup> mice had less neointima formation compared with ApoE<sup>−/−</sup> littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm<sup>2</sup>, <em>P</em> = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm<sup>2</sup>, <em>P</em> = 0.043). <p><em><strong>Conclusion</strong></em></p> Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting. |
| first_indexed | 2024-03-06T20:39:32Z |
| format | Journal article |
| id | oxford-uuid:33cc5541-63a7-4f15-9055-270ccae1c9bd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:39:32Z |
| publishDate | 2013 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:33cc5541-63a7-4f15-9055-270ccae1c9bd2022-03-26T13:22:18ZEndothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:33cc5541-63a7-4f15-9055-270ccae1c9bdEnglishSymplectic Elements at OxfordOxford University Press2013Douglas, GVan Kampen, EHale, AMcNeill, EPatel, JCrabtree, MAli, ZHoerr, RAlp, NChannon, K<p><em><strong>Aims</strong></em></p> Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. <p><em><strong>Methods and results</strong></em></p> Endothelial cell repopulation was assessed en face in stented arteries in ApoE<sup>−/−</sup> mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm<sup>2</sup>, <em>P</em> = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm<sup>2</sup>, <em>P</em> = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE<sup>−/−</sup> mice had less neointima formation compared with ApoE<sup>−/−</sup> littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm<sup>2</sup>, <em>P</em> = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm<sup>2</sup>, <em>P</em> = 0.043). <p><em><strong>Conclusion</strong></em></p> Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting. |
| spellingShingle | Douglas, G Van Kampen, E Hale, A McNeill, E Patel, J Crabtree, M Ali, Z Hoerr, R Alp, N Channon, K Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title | Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title_full | Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title_fullStr | Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title_full_unstemmed | Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title_short | Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification. |
| title_sort | endothelial cell repopulation after stenting determines in stent neointima formation effects of bare metal vs drug eluting stents and genetic endothelial cell modification |
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