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Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis

Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligati...

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Autores principales: Kolega, John, Poppenberg, Kerry E., Lim, Hee-Woong, Gutierrez, Liza C., Veeturi, Sricharan S., Siddiqui, Adnan H., Rajabzadeh-Oghaz, Hamidreza, Tutino, Vincent M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352890/
https://www.ncbi.nlm.nih.gov/pubmed/34373496
http://dx.doi.org/10.1038/s41598-021-95403-x
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author Kolega, John
Poppenberg, Kerry E.
Lim, Hee-Woong
Gutierrez, Liza C.
Veeturi, Sricharan S.
Siddiqui, Adnan H.
Rajabzadeh-Oghaz, Hamidreza
Tutino, Vincent M.
author_facet Kolega, John
Poppenberg, Kerry E.
Lim, Hee-Woong
Gutierrez, Liza C.
Veeturi, Sricharan S.
Siddiqui, Adnan H.
Rajabzadeh-Oghaz, Hamidreza
Tutino, Vincent M.
author_sort Kolega, John
collection PubMed
description Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling.
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spelling pubmed-83528902021-08-10 Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis Kolega, John Poppenberg, Kerry E. Lim, Hee-Woong Gutierrez, Liza C. Veeturi, Sricharan S. Siddiqui, Adnan H. Rajabzadeh-Oghaz, Hamidreza Tutino, Vincent M. Sci Rep Article Changes in blood flow can induce arterial remodeling. Intimal cells sense flow and send signals to the media to initiate remodeling. However, the nature of such intima-media signaling is not fully understood. To identify potential signals, New Zealand white rabbits underwent bilateral carotid ligation to increase flow in the basilar artery or sham surgery (n = 2 ligated, n = 2 sham). Flow was measured by transcranial Doppler ultrasonography, vessel geometry was determined by 3D angiography, and hemodynamics were quantified by computational fluid dynamics. 24 h post-surgery, the basilar artery and terminus were embedded for sectioning. Intima and media were separately microdissected from the sections, and whole transcriptomes were obtained by RNA-seq. Correlation analysis of expression across all possible intima-media gene pairs revealed potential remodeling signals. Carotid ligation increased flow in the basilar artery and terminus and caused differential expression of 194 intimal genes and 529 medial genes. 29,777 intima-media gene pairs exhibited correlated expression. 18 intimal genes had > 200 medial correlates and coded for extracellular products. Gene ontology of the medial correlates showed enrichment of organonitrogen metabolism, leukocyte activation/immune response, and secretion/exocytosis processes. This demonstrates correlative expression analysis of intimal and medial genes can reveal novel signals that may regulate flow-induced arterial remodeling. Nature Publishing Group UK 2021-08-09 /pmc/articles/PMC8352890/ /pubmed/34373496 http://dx.doi.org/10.1038/s41598-021-95403-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kolega, John
Poppenberg, Kerry E.
Lim, Hee-Woong
Gutierrez, Liza C.
Veeturi, Sricharan S.
Siddiqui, Adnan H.
Rajabzadeh-Oghaz, Hamidreza
Tutino, Vincent M.
Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title_full Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title_fullStr Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title_full_unstemmed Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title_short Identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
title_sort identification of intima-to-media signals for flow-induced vascular remodeling using correlative gene expression analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352890/
https://www.ncbi.nlm.nih.gov/pubmed/34373496
http://dx.doi.org/10.1038/s41598-021-95403-x
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