Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Clapp, Averill, Shawber, Carrie J., Wu, June K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
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
_version_ 1785100191521570816
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
work_keys_str_mv AT clappaverill pathophysiologyofslowflowvascularmalformationscurrentunderstandingandunansweredquestions
AT shawbercarriej pathophysiologyofslowflowvascularmalformationscurrentunderstandingandunansweredquestions
AT wujunek pathophysiologyofslowflowvascularmalformationscurrentunderstandingandunansweredquestions