Faculty Collaboration Database

RhoA activation-mediated vascular permeability in capillary malformation-arteriovenous malformation syndrome: a hypothesis. Drug Discov Today 2021 Aug;26(8):1790-1793

Date

12/29/2020

Pubmed ID

33358701

DOI

10.1016/j.drudis.2020.12.012

Scopus ID

2-s2.0-85098655506 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a class of capillary anomalies that are associated with arteriovenous malformations and arteriovenous fistulas, which carry a risk of hemorrhages. There are no broadly effective pharmacological therapies currently available. Most CM-AVMs are associated with a loss of RASA1, resulting in constitutive activation of RAS signaling. However, protein interaction analysis revealed that RASA1 forms a complex with Rho GTPase-activating protein (RhoGAP), a negative regulator of RhoA signaling. Herein, we propose that loss of RASA1 function results in constitutive activation of RhoA signaling in endothelial cells, resulting in enhanced vascular permeability. Therefore, strategies aimed at curtailing RhoA activity should be tested as an adjunctive therapeutic approach in cell culture studies and animal models of RASA1 deficiency.

Author List

Eisa-Beygi S, Vo NJ, Link BA

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arteriovenous Malformations
Capillaries
Capillary Permeability
Endothelial Cells
Humans
Mutation
Port-Wine Stain
Signal Transduction
p120 GTPase Activating Protein
rhoA GTP-Binding Protein