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Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling
The distinct topographic Hox expression patterns observed in vascular smooth muscle cells (VSMCs) of the adult cardiovascular system suggest that these transcriptional regulators are critical for maintaining region-specific physiological properties of blood vessels. To test this proposition, we expa...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507213/ https://www.ncbi.nlm.nih.gov/pubmed/23213434 http://dx.doi.org/10.1242/bio.2012039 |
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author | Pruett, Nathanael D. Hajdu, Zoltan Zhang, Jing Visconti, Richard P. Kern, Michael J. Wellik, Deneen M. Majesky, Mark W. Awgulewitsch, Alexander |
author_facet | Pruett, Nathanael D. Hajdu, Zoltan Zhang, Jing Visconti, Richard P. Kern, Michael J. Wellik, Deneen M. Majesky, Mark W. Awgulewitsch, Alexander |
author_sort | Pruett, Nathanael D. |
collection | PubMed |
description | The distinct topographic Hox expression patterns observed in vascular smooth muscle cells (VSMCs) of the adult cardiovascular system suggest that these transcriptional regulators are critical for maintaining region-specific physiological properties of blood vessels. To test this proposition, we expanded the vascular Hoxc11 expression domain normally restricted to the lower limbs by utilizing an innovative integrated tetracycline regulatory system and Transgelin promoter elements to induce Hoxc11 expression universally in VSMCs of transgenic mice. Ectopic Hoxc11 expression in carotid arteries, aortic arch and descending aorta resulted in drastic vessel wall remodeling involving elastic laminae fragmentation, medial smooth muscle cell loss, and intimal lesion formation. None of these alterations were observed upon induction of Hoxc11 transgene expression in the femoral artery, i.e. the natural Hoxc11 activity domain, although this vessel was greatly enlarged, comparable to the topographically restricted vascular changes seen in Hoxc11(−/−) mice. To begin defining Hoxc11-controlled pathways of vascular remodeling, we performed immunolabeling studies in conjunction with co-transfection and chromatin immunoprecipitation (ChIP) assays using mouse vascular smooth muscle (MOVAS) cells. The results suggest direct transcriptional control of two members of the matrix metalloproteinase (Mmp) family, including Mmp2 and Mmp9 that are known as key players in the inception and progression of vascular remodeling events. In summary, the severe vascular abnormalities resulting from the induced dysregulated expression of a Hox gene with regional vascular patterning functions suggest that proper Hox function and regulation is critical for maintaining vascular functional integrity. |
format | Online Article Text |
id | pubmed-3507213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-35072132012-12-04 Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling Pruett, Nathanael D. Hajdu, Zoltan Zhang, Jing Visconti, Richard P. Kern, Michael J. Wellik, Deneen M. Majesky, Mark W. Awgulewitsch, Alexander Biol Open Research Article The distinct topographic Hox expression patterns observed in vascular smooth muscle cells (VSMCs) of the adult cardiovascular system suggest that these transcriptional regulators are critical for maintaining region-specific physiological properties of blood vessels. To test this proposition, we expanded the vascular Hoxc11 expression domain normally restricted to the lower limbs by utilizing an innovative integrated tetracycline regulatory system and Transgelin promoter elements to induce Hoxc11 expression universally in VSMCs of transgenic mice. Ectopic Hoxc11 expression in carotid arteries, aortic arch and descending aorta resulted in drastic vessel wall remodeling involving elastic laminae fragmentation, medial smooth muscle cell loss, and intimal lesion formation. None of these alterations were observed upon induction of Hoxc11 transgene expression in the femoral artery, i.e. the natural Hoxc11 activity domain, although this vessel was greatly enlarged, comparable to the topographically restricted vascular changes seen in Hoxc11(−/−) mice. To begin defining Hoxc11-controlled pathways of vascular remodeling, we performed immunolabeling studies in conjunction with co-transfection and chromatin immunoprecipitation (ChIP) assays using mouse vascular smooth muscle (MOVAS) cells. The results suggest direct transcriptional control of two members of the matrix metalloproteinase (Mmp) family, including Mmp2 and Mmp9 that are known as key players in the inception and progression of vascular remodeling events. In summary, the severe vascular abnormalities resulting from the induced dysregulated expression of a Hox gene with regional vascular patterning functions suggest that proper Hox function and regulation is critical for maintaining vascular functional integrity. The Company of Biologists 2012-03-20 /pmc/articles/PMC3507213/ /pubmed/23213434 http://dx.doi.org/10.1242/bio.2012039 Text en © 2012. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Article Pruett, Nathanael D. Hajdu, Zoltan Zhang, Jing Visconti, Richard P. Kern, Michael J. Wellik, Deneen M. Majesky, Mark W. Awgulewitsch, Alexander Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title | Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title_full | Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title_fullStr | Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title_full_unstemmed | Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title_short | Changing topographic Hox expression in blood vessels results in regionally distinct vessel wall remodeling |
title_sort | changing topographic hox expression in blood vessels results in regionally distinct vessel wall remodeling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507213/ https://www.ncbi.nlm.nih.gov/pubmed/23213434 http://dx.doi.org/10.1242/bio.2012039 |
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