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Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change

Experimental data indicate that the adventitial compartment of blood vessels, in both the pulmonary and systemic circulations, like the connective tissue stroma in tissues throughout the body, is a critical regulator of vessel wall function in health and disease. It is clear that adventitial cells,...

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Autores principales: Stenmark, Kurt R., Frid, Maria G., Yeager, Michael, Li, Min, Riddle, Suzette, McKinsey, Timothy, El Kasmi, Karim C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342746/
https://www.ncbi.nlm.nih.gov/pubmed/22558514
http://dx.doi.org/10.4103/2045-8932.94817
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author Stenmark, Kurt R.
Frid, Maria G.
Yeager, Michael
Li, Min
Riddle, Suzette
McKinsey, Timothy
El Kasmi, Karim C.
author_facet Stenmark, Kurt R.
Frid, Maria G.
Yeager, Michael
Li, Min
Riddle, Suzette
McKinsey, Timothy
El Kasmi, Karim C.
author_sort Stenmark, Kurt R.
collection PubMed
description Experimental data indicate that the adventitial compartment of blood vessels, in both the pulmonary and systemic circulations, like the connective tissue stroma in tissues throughout the body, is a critical regulator of vessel wall function in health and disease. It is clear that adventitial cells, and in particular the adventitial fibroblast, are activated early following vascular injury, and play essential roles in regulating vascular wall structure and function through production of chemokines, cytokines, growth factors, and reactive oxygen species (ROS). The recognition of the ability of these cells to generate and maintain inflammatory responses within the vessel wall provides insight into why vascular inflammatory responses, in certain situations, fail to resolve. It is also clear that the activated adventitial fibroblast plays an important role in regulating vasa vasorum growth, which can contribute to ongoing vascular remodeling by acting as a conduit for delivery of inflammatory and progenitor cells. These functions of the fibroblast clearly support the idea that targeting chemokine, cytokine, adhesion molecule, and growth factor production in activated fibroblasts could be helpful in abrogating vascular inflammatory responses and thus in ameliorating vascular disease. Further, the recent observations that fibroblasts in vascular and fibrotic diseases may maintain their activated state through epigenetic alterations in key inflammatory and pro-fibrotic genes suggests that current therapies used to treat pulmonary hypertension may not be sufficient to induce apoptosis or to inhibit key inflammatory signaling pathways in these fibroblasts. New therapies targeted at reversing changes in the acetylation or methylation status of key transcriptional networks may be needed. At present, therapies specifically targeting abnormalities of histone deacytelase (HDAC) activity in fibroblast-like cells appear to hold promise.
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spelling pubmed-33427462012-05-03 Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change Stenmark, Kurt R. Frid, Maria G. Yeager, Michael Li, Min Riddle, Suzette McKinsey, Timothy El Kasmi, Karim C. Pulm Circ Review Article Experimental data indicate that the adventitial compartment of blood vessels, in both the pulmonary and systemic circulations, like the connective tissue stroma in tissues throughout the body, is a critical regulator of vessel wall function in health and disease. It is clear that adventitial cells, and in particular the adventitial fibroblast, are activated early following vascular injury, and play essential roles in regulating vascular wall structure and function through production of chemokines, cytokines, growth factors, and reactive oxygen species (ROS). The recognition of the ability of these cells to generate and maintain inflammatory responses within the vessel wall provides insight into why vascular inflammatory responses, in certain situations, fail to resolve. It is also clear that the activated adventitial fibroblast plays an important role in regulating vasa vasorum growth, which can contribute to ongoing vascular remodeling by acting as a conduit for delivery of inflammatory and progenitor cells. These functions of the fibroblast clearly support the idea that targeting chemokine, cytokine, adhesion molecule, and growth factor production in activated fibroblasts could be helpful in abrogating vascular inflammatory responses and thus in ameliorating vascular disease. Further, the recent observations that fibroblasts in vascular and fibrotic diseases may maintain their activated state through epigenetic alterations in key inflammatory and pro-fibrotic genes suggests that current therapies used to treat pulmonary hypertension may not be sufficient to induce apoptosis or to inhibit key inflammatory signaling pathways in these fibroblasts. New therapies targeted at reversing changes in the acetylation or methylation status of key transcriptional networks may be needed. At present, therapies specifically targeting abnormalities of histone deacytelase (HDAC) activity in fibroblast-like cells appear to hold promise. Medknow Publications & Media Pvt Ltd 2012 /pmc/articles/PMC3342746/ /pubmed/22558514 http://dx.doi.org/10.4103/2045-8932.94817 Text en Copyright: © Pulmonary Circulation http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Stenmark, Kurt R.
Frid, Maria G.
Yeager, Michael
Li, Min
Riddle, Suzette
McKinsey, Timothy
El Kasmi, Karim C.
Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title_full Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title_fullStr Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title_full_unstemmed Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title_short Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change
title_sort targeting the adventitial microenvironment in pulmonary hypertension: a potential approach to therapy that considers epigenetic change
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342746/
https://www.ncbi.nlm.nih.gov/pubmed/22558514
http://dx.doi.org/10.4103/2045-8932.94817
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