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Arterial dissections: Common features and new perspectives

Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary,...

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Autores principales: Bax, Monique, Romanov, Valentin, Junday, Keerat, Giannoulatou, Eleni, Martinac, Boris, Kovacic, Jason C., Liu, Renjing, Iismaa, Siiri E., Graham, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763901/
https://www.ncbi.nlm.nih.gov/pubmed/36561772
http://dx.doi.org/10.3389/fcvm.2022.1055862
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author Bax, Monique
Romanov, Valentin
Junday, Keerat
Giannoulatou, Eleni
Martinac, Boris
Kovacic, Jason C.
Liu, Renjing
Iismaa, Siiri E.
Graham, Robert M.
author_facet Bax, Monique
Romanov, Valentin
Junday, Keerat
Giannoulatou, Eleni
Martinac, Boris
Kovacic, Jason C.
Liu, Renjing
Iismaa, Siiri E.
Graham, Robert M.
author_sort Bax, Monique
collection PubMed
description Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations – such as stroke, myocardial infarction, and renal failure. Here, we review the shared and unique features of these arteriopathies to provide a better understanding of this family of disorders. Arterial dissections occur commonly in the young to middle-aged, and often in conjunction with hypertension and/or migraine; the latter suggesting they are part of a generalized vasculopathy. Genetic studies as well as cellular and molecular investigations of arterial dissections reveal striking similarities between dissection types, particularly their pathophysiology, which includes the presence or absence of an intimal tear and vasa vasorum dysfunction as a cause of intramural hemorrhage. Pathway perturbations common to all types of dissections include disruption of TGF-β signaling, the extracellular matrix, the cytoskeleton or metabolism, as evidenced by the finding of mutations in critical genes regulating these processes, including LRP1, collagen genes, fibrillin and TGF-β receptors, or their coupled pathways. Perturbances in these connected signaling pathways contribute to phenotype switching in endothelial and vascular smooth muscle cells of the affected artery, in which their physiological quiescent state is lost and replaced by a proliferative activated phenotype. Of interest, dissections in various anatomical locations are associated with distinct sex and age predilections, suggesting involvement of gene and environment interactions in disease pathogenesis. Importantly, these cellular mechanisms are potentially therapeutically targetable. Consideration of arterial dissections as a collective pathology allows insight from the better characterized dissection types, such as that involving the thoracic aorta, to be leveraged to inform the less common forms of dissections, including the potential to apply known therapeutic interventions already clinically available for the former.
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spelling pubmed-97639012022-12-21 Arterial dissections: Common features and new perspectives Bax, Monique Romanov, Valentin Junday, Keerat Giannoulatou, Eleni Martinac, Boris Kovacic, Jason C. Liu, Renjing Iismaa, Siiri E. Graham, Robert M. Front Cardiovasc Med Cardiovascular Medicine Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations – such as stroke, myocardial infarction, and renal failure. Here, we review the shared and unique features of these arteriopathies to provide a better understanding of this family of disorders. Arterial dissections occur commonly in the young to middle-aged, and often in conjunction with hypertension and/or migraine; the latter suggesting they are part of a generalized vasculopathy. Genetic studies as well as cellular and molecular investigations of arterial dissections reveal striking similarities between dissection types, particularly their pathophysiology, which includes the presence or absence of an intimal tear and vasa vasorum dysfunction as a cause of intramural hemorrhage. Pathway perturbations common to all types of dissections include disruption of TGF-β signaling, the extracellular matrix, the cytoskeleton or metabolism, as evidenced by the finding of mutations in critical genes regulating these processes, including LRP1, collagen genes, fibrillin and TGF-β receptors, or their coupled pathways. Perturbances in these connected signaling pathways contribute to phenotype switching in endothelial and vascular smooth muscle cells of the affected artery, in which their physiological quiescent state is lost and replaced by a proliferative activated phenotype. Of interest, dissections in various anatomical locations are associated with distinct sex and age predilections, suggesting involvement of gene and environment interactions in disease pathogenesis. Importantly, these cellular mechanisms are potentially therapeutically targetable. Consideration of arterial dissections as a collective pathology allows insight from the better characterized dissection types, such as that involving the thoracic aorta, to be leveraged to inform the less common forms of dissections, including the potential to apply known therapeutic interventions already clinically available for the former. Frontiers Media S.A. 2022-12-06 /pmc/articles/PMC9763901/ /pubmed/36561772 http://dx.doi.org/10.3389/fcvm.2022.1055862 Text en Copyright © 2022 Bax, Romanov, Junday, Giannoulatou, Martinac, Kovacic, Liu, Iismaa and Graham. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Bax, Monique
Romanov, Valentin
Junday, Keerat
Giannoulatou, Eleni
Martinac, Boris
Kovacic, Jason C.
Liu, Renjing
Iismaa, Siiri E.
Graham, Robert M.
Arterial dissections: Common features and new perspectives
title Arterial dissections: Common features and new perspectives
title_full Arterial dissections: Common features and new perspectives
title_fullStr Arterial dissections: Common features and new perspectives
title_full_unstemmed Arterial dissections: Common features and new perspectives
title_short Arterial dissections: Common features and new perspectives
title_sort arterial dissections: common features and new perspectives
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763901/
https://www.ncbi.nlm.nih.gov/pubmed/36561772
http://dx.doi.org/10.3389/fcvm.2022.1055862
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