VEGF signaling regulates the fate of obstructed capillaries in mouse cortex
Cortical capillaries are prone to obstruction, which over time, could have a major impact on brain angioarchitecture and function. The mechanisms that govern the removal of these obstructions and what long-term fate awaits obstructed capillaries, remains a mystery. We estimate that ~0.12% of mouse c...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/33670 |
| _version_ | 1811181075039256576 |
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| author | Patrick Reeson Kevin Choi Craig E Brown |
| author_facet | Patrick Reeson Kevin Choi Craig E Brown |
| author_sort | Patrick Reeson |
| collection | DOAJ |
| description | Cortical capillaries are prone to obstruction, which over time, could have a major impact on brain angioarchitecture and function. The mechanisms that govern the removal of these obstructions and what long-term fate awaits obstructed capillaries, remains a mystery. We estimate that ~0.12% of mouse cortical capillaries are obstructed each day (lasting >20 min), preferentially in superficial layers and lower order branches. Tracking natural or microsphere-induced obstructions revealed that 75–80% of capillaries recanalized within 24 hr. Remarkably, 30% of all obstructed capillaries were pruned by 21 days, including some that had regained flow. Pruning involved regression of endothelial cells, which was not compensated for by sprouting. Using this information, we predicted capillary loss with aging that closely matched experimental estimates. Genetic knockdown or inhibition of VEGF-R2 signaling was a critical factor in promoting capillary recanalization and minimizing subsequent pruning. Our studies reveal the incidence, mechanism and long-term outcome of capillary obstructions which can also explain age-related capillary rarefaction. |
| first_indexed | 2024-04-11T09:13:37Z |
| format | Article |
| id | doaj.art-2ac45c44aca74c51ab053141c81d6854 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:37Z |
| publishDate | 2018-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2ac45c44aca74c51ab053141c81d68542022-12-22T04:32:26ZengeLife Sciences Publications LtdeLife2050-084X2018-04-01710.7554/eLife.33670VEGF signaling regulates the fate of obstructed capillaries in mouse cortexPatrick Reeson0Kevin Choi1Craig E Brown2https://orcid.org/0000-0002-0076-2414Division of Medical Sciences, University of Victoria, Victoria, CanadaDivision of Medical Sciences, University of Victoria, Victoria, CanadaDivision of Medical Sciences, University of Victoria, Victoria, Canada; Department of Biology, University of Victoria, Victoria, Canada; Department of Psychiatry, University of British Columbia, Vancouver, CanadaCortical capillaries are prone to obstruction, which over time, could have a major impact on brain angioarchitecture and function. The mechanisms that govern the removal of these obstructions and what long-term fate awaits obstructed capillaries, remains a mystery. We estimate that ~0.12% of mouse cortical capillaries are obstructed each day (lasting >20 min), preferentially in superficial layers and lower order branches. Tracking natural or microsphere-induced obstructions revealed that 75–80% of capillaries recanalized within 24 hr. Remarkably, 30% of all obstructed capillaries were pruned by 21 days, including some that had regained flow. Pruning involved regression of endothelial cells, which was not compensated for by sprouting. Using this information, we predicted capillary loss with aging that closely matched experimental estimates. Genetic knockdown or inhibition of VEGF-R2 signaling was a critical factor in promoting capillary recanalization and minimizing subsequent pruning. Our studies reveal the incidence, mechanism and long-term outcome of capillary obstructions which can also explain age-related capillary rarefaction.https://elifesciences.org/articles/33670capillaryagingVEGFvascular dementia |
| spellingShingle | Patrick Reeson Kevin Choi Craig E Brown VEGF signaling regulates the fate of obstructed capillaries in mouse cortex eLife capillary aging VEGF vascular dementia |
| title | VEGF signaling regulates the fate of obstructed capillaries in mouse cortex |
| title_full | VEGF signaling regulates the fate of obstructed capillaries in mouse cortex |
| title_fullStr | VEGF signaling regulates the fate of obstructed capillaries in mouse cortex |
| title_full_unstemmed | VEGF signaling regulates the fate of obstructed capillaries in mouse cortex |
| title_short | VEGF signaling regulates the fate of obstructed capillaries in mouse cortex |
| title_sort | vegf signaling regulates the fate of obstructed capillaries in mouse cortex |
| topic | capillary aging VEGF vascular dementia |
| url | https://elifesciences.org/articles/33670 |
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