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Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart
AIMS: Capillary and arterial endothelial cells share many common molecular markers in both the neonatal and adult hearts. Herein, we aim to establish a genetic tool that distinguishes these two types of vessels in order to determine the cellular mechanism underlying collateral artery formation. METH...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752045/ https://www.ncbi.nlm.nih.gov/pubmed/26768261 http://dx.doi.org/10.1093/cvr/cvw005 |
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author | He, Lingjuan Liu, Qiaozhen Hu, Tianyuan Huang, Xiuzhen Zhang, Hui Tian, Xueying Yan, Yan Wang, Li Huang, Yu Miquerol, Lucile Wythe, Joshua D. Zhou, Bin |
author_facet | He, Lingjuan Liu, Qiaozhen Hu, Tianyuan Huang, Xiuzhen Zhang, Hui Tian, Xueying Yan, Yan Wang, Li Huang, Yu Miquerol, Lucile Wythe, Joshua D. Zhou, Bin |
author_sort | He, Lingjuan |
collection | PubMed |
description | AIMS: Capillary and arterial endothelial cells share many common molecular markers in both the neonatal and adult hearts. Herein, we aim to establish a genetic tool that distinguishes these two types of vessels in order to determine the cellular mechanism underlying collateral artery formation. METHODS AND RESULTS: Using Apln-GFP and Apln-LacZ reporter mice, we demonstrate that APLN expression is enriched in coronary vascular endothelial cells. However, APLN expression is reduced in coronary arterial endothelial cells. Genetic lineage tracing, using an Apln-CreER mouse line, robustly labelled capillary endothelial cells, but not arterial endothelial cells. We leveraged this differential activity of Apln-CreER to study collateral artery formation following myocardial infarction (MI). In a neonatal heart MI model, we found that Apln-CreER-labelled capillary endothelial cells do not contribute to the large collateral arteries. Instead, these large collateral arteries mainly arise from pre-existing, infrequently labelled coronary arteries, indicative of arteriogenesis. Furthermore, in an adult heart MI model, Apln-CreER activity also distinguishes large and small diameter arteries from capillaries. Lineage tracing in this setting demonstrated that most large and small coronary arteries in the infarcted myocardium and border region are derived not from capillaries, but from pre-existing arteries. CONCLUSION: Apln-CreER-mediated lineage tracing distinguishes capillaries from large arteries, in both the neonatal and adult hearts. Through genetic fate mapping, we demonstrate that pre-existing arteries, but not capillaries, extensively contribute to collateral artery formation following myocardial injury. These results suggest that arteriogenesis is the major mechanism underlying collateral vessel formation. |
format | Online Article Text |
id | pubmed-4752045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47520452016-02-16 Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart He, Lingjuan Liu, Qiaozhen Hu, Tianyuan Huang, Xiuzhen Zhang, Hui Tian, Xueying Yan, Yan Wang, Li Huang, Yu Miquerol, Lucile Wythe, Joshua D. Zhou, Bin Cardiovasc Res ORIGINAL ARTICLES AIMS: Capillary and arterial endothelial cells share many common molecular markers in both the neonatal and adult hearts. Herein, we aim to establish a genetic tool that distinguishes these two types of vessels in order to determine the cellular mechanism underlying collateral artery formation. METHODS AND RESULTS: Using Apln-GFP and Apln-LacZ reporter mice, we demonstrate that APLN expression is enriched in coronary vascular endothelial cells. However, APLN expression is reduced in coronary arterial endothelial cells. Genetic lineage tracing, using an Apln-CreER mouse line, robustly labelled capillary endothelial cells, but not arterial endothelial cells. We leveraged this differential activity of Apln-CreER to study collateral artery formation following myocardial infarction (MI). In a neonatal heart MI model, we found that Apln-CreER-labelled capillary endothelial cells do not contribute to the large collateral arteries. Instead, these large collateral arteries mainly arise from pre-existing, infrequently labelled coronary arteries, indicative of arteriogenesis. Furthermore, in an adult heart MI model, Apln-CreER activity also distinguishes large and small diameter arteries from capillaries. Lineage tracing in this setting demonstrated that most large and small coronary arteries in the infarcted myocardium and border region are derived not from capillaries, but from pre-existing arteries. CONCLUSION: Apln-CreER-mediated lineage tracing distinguishes capillaries from large arteries, in both the neonatal and adult hearts. Through genetic fate mapping, we demonstrate that pre-existing arteries, but not capillaries, extensively contribute to collateral artery formation following myocardial injury. These results suggest that arteriogenesis is the major mechanism underlying collateral vessel formation. Oxford University Press 2016-03-01 2016-01-13 /pmc/articles/PMC4752045/ /pubmed/26768261 http://dx.doi.org/10.1093/cvr/cvw005 Text en © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | ORIGINAL ARTICLES He, Lingjuan Liu, Qiaozhen Hu, Tianyuan Huang, Xiuzhen Zhang, Hui Tian, Xueying Yan, Yan Wang, Li Huang, Yu Miquerol, Lucile Wythe, Joshua D. Zhou, Bin Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title | Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title_full | Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title_fullStr | Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title_full_unstemmed | Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title_short | Genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
title_sort | genetic lineage tracing discloses arteriogenesis as the main mechanism for collateral growth in the mouse heart |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752045/ https://www.ncbi.nlm.nih.gov/pubmed/26768261 http://dx.doi.org/10.1093/cvr/cvw005 |
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