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Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases

In contrast with the heart, the adult mammalian vasculature retains significant remodelling capacity, dysregulation of which is implicated in disease development. In particular, vascular smooth muscle cells (VSMCs) play major roles in the pathological vascular remodelling characteristic of atheroscl...

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Autores principales: Worssam, Matthew D., Jørgensen, Helle F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589433/
https://www.ncbi.nlm.nih.gov/pubmed/34495326
http://dx.doi.org/10.1042/BST20210138
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author Worssam, Matthew D.
Jørgensen, Helle F.
author_facet Worssam, Matthew D.
Jørgensen, Helle F.
author_sort Worssam, Matthew D.
collection PubMed
description In contrast with the heart, the adult mammalian vasculature retains significant remodelling capacity, dysregulation of which is implicated in disease development. In particular, vascular smooth muscle cells (VSMCs) play major roles in the pathological vascular remodelling characteristic of atherosclerosis, restenosis, aneurysm and pulmonary arterial hypertension. Clonal lineage tracing revealed that the VSMC-contribution to disease results from the hyperproliferation of few pre-existing medial cells and suggested that VSMC-derived cells from the same clone can adopt diverse phenotypes. Studies harnessing the powerful combination of lineage tracing and single-cell transcriptomics have delineated the substantial diversity of VSMC-derived cells in vascular lesions, which are proposed to have both beneficial and detrimental effects on disease severity. Computational analyses further suggest that the pathway from contractile VSMCs in healthy arteries to phenotypically distinct lesional cells consists of multiple, potentially regulatable, steps. A better understanding of how individual steps are controlled could reveal effective therapeutic strategies to minimise VSMC functions that drive pathology whilst maintaining or enhancing their beneficial roles. Here we review current knowledge of VSMC plasticity and highlight important questions that should be addressed to understand how specific stages of VSMC investment and phenotypic diversification are controlled. Implications for developing therapeutic strategies in pathological vascular remodelling are discussed and we explore how cutting-edge approaches could be used to elucidate the molecular mechanisms underlying VSMC regulation.
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spelling pubmed-85894332021-11-18 Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases Worssam, Matthew D. Jørgensen, Helle F. Biochem Soc Trans Review Articles In contrast with the heart, the adult mammalian vasculature retains significant remodelling capacity, dysregulation of which is implicated in disease development. In particular, vascular smooth muscle cells (VSMCs) play major roles in the pathological vascular remodelling characteristic of atherosclerosis, restenosis, aneurysm and pulmonary arterial hypertension. Clonal lineage tracing revealed that the VSMC-contribution to disease results from the hyperproliferation of few pre-existing medial cells and suggested that VSMC-derived cells from the same clone can adopt diverse phenotypes. Studies harnessing the powerful combination of lineage tracing and single-cell transcriptomics have delineated the substantial diversity of VSMC-derived cells in vascular lesions, which are proposed to have both beneficial and detrimental effects on disease severity. Computational analyses further suggest that the pathway from contractile VSMCs in healthy arteries to phenotypically distinct lesional cells consists of multiple, potentially regulatable, steps. A better understanding of how individual steps are controlled could reveal effective therapeutic strategies to minimise VSMC functions that drive pathology whilst maintaining or enhancing their beneficial roles. Here we review current knowledge of VSMC plasticity and highlight important questions that should be addressed to understand how specific stages of VSMC investment and phenotypic diversification are controlled. Implications for developing therapeutic strategies in pathological vascular remodelling are discussed and we explore how cutting-edge approaches could be used to elucidate the molecular mechanisms underlying VSMC regulation. Portland Press Ltd. 2021-11-01 2021-09-08 /pmc/articles/PMC8589433/ /pubmed/34495326 http://dx.doi.org/10.1042/BST20210138 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University of Cambridge in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.
spellingShingle Review Articles
Worssam, Matthew D.
Jørgensen, Helle F.
Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title_full Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title_fullStr Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title_full_unstemmed Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title_short Mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
title_sort mechanisms of vascular smooth muscle cell investment and phenotypic diversification in vascular diseases
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589433/
https://www.ncbi.nlm.nih.gov/pubmed/34495326
http://dx.doi.org/10.1042/BST20210138
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