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Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions
BACKGROUND: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473035/ https://www.ncbi.nlm.nih.gov/pubmed/37662560 http://dx.doi.org/10.1097/JOVA.0000000000000069 |
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author | Clapp, Averill Shawber, Carrie J. Wu, June K. |
author_facet | Clapp, Averill Shawber, Carrie J. Wu, June K. |
author_sort | Clapp, Averill |
collection | PubMed |
description | BACKGROUND: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. METHODS: A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms “venous malformation,” “lymphatic malformation,” “lymphaticovenous malformation,” “genetic variant,” “genetic mutation,” “endothelial cells,” and “animal model.” Relevant publications were reviewed and summarized. RESULTS: The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments. CONCLUSION: Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features. |
format | Online Article Text |
id | pubmed-10473035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-104730352023-09-02 Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions Clapp, Averill Shawber, Carrie J. Wu, June K. J Vasc Anom (Phila) Evidence-Based Reviews BACKGROUND: Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. METHODS: A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms “venous malformation,” “lymphatic malformation,” “lymphaticovenous malformation,” “genetic variant,” “genetic mutation,” “endothelial cells,” and “animal model.” Relevant publications were reviewed and summarized. RESULTS: The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments. CONCLUSION: Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features. Lippincott Williams & Wilkins 2023-07-10 /pmc/articles/PMC10473035/ /pubmed/37662560 http://dx.doi.org/10.1097/JOVA.0000000000000069 Text en Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The International Society for the Study of Vascular Anomalies. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Evidence-Based Reviews Clapp, Averill Shawber, Carrie J. Wu, June K. Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title | Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title_full | Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title_fullStr | Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title_full_unstemmed | Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title_short | Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions |
title_sort | pathophysiology of slow-flow vascular malformations: current understanding and unanswered questions |
topic | Evidence-Based Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473035/ https://www.ncbi.nlm.nih.gov/pubmed/37662560 http://dx.doi.org/10.1097/JOVA.0000000000000069 |
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