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Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation.

ABSTRACT: Objectives: Arteriovenous malformation (AVM) consists of a nidus with poorly formed low-resistance vessels in place of a functional capillary network. The role of somatic mutations in embryonic stem cells (ESCs) and vascular anomalies and the presence of primitive populations in vascular anomalies led us to investigate the presence of a primitive population in extracranial AVM. Methods: Extracranial AVM tissue samples from 12 patients were stained for stemness-associated markers OCT4, SOX2, NANOG, KLF4, and c-MYC using immunohistochemical staining. In situ hybridization (ISH) was performed on six tissue samples to determine transcript expression. Western blotting and RT-qPCR were performed on two AVM-derived primary cell lines to determine protein and transcript expression of these markers, respectively. Immunofluorescence staining was performed on two tissue samples to investigate marker co-localization. Results: Immunohistochemical staining demonstrated the expression of OCT4, SOX2, KLF4, and c-MYC on the endothelium and media of lesional vessels and cells within the stroma of the nidus in all 12 AVM tissue samples. ISH and RT-qPCR confirmed transcript expression of all five markers. Western blotting showed protein expression of all markers except NANOG. Immunofluorescence staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ population within the endothelium and media of the lesional vessels and cells within the stroma of the AVM nidus. Conclusions: Our findings may suggest the presence of a primitive population within the AVM nidus. Further investigation may lead to novel therapeutic targeting of this population.

SUBMITTER: Luke Krishnan CS

PROVIDER: S-EPMC8017302 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Pulmonary arteriovenous malformations are abnormal direct connections between the pulmonary artery and pulmonary vein which result in a right-to-left shunt. They are associated with substantial morbidity and mortality mainly from the effects of paradoxical emboli. Potential complications include stroke, cerebral abscess, pulmonary haemorrhage and hypoxaemia. Embolisation is an endovascular intervention based on the occlusion of the feeding arteries the pulmonary arteriovenous malformations thus eliminating the abnormal right-to-left-shunting. This is an update of a previously published review. OBJECTIVES:To determine the efficacy and safety of embolisation in patients with pulmonary arteriovenous malformations including a comparison with surgical resection and different embolisation devices. SEARCH METHODS:We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register; date of last search: 10 April 2017.We also searched the following databases: the Australian New Zealand Clinical Trials Registry; ClinicalTrials.gov; International Standard Randomised Controlled Trial Number Register; International Clinical Trials Registry Platform Search Portal (last searched 27 August 2017). to be updatedWe checked cross-references and searched references from review articles. SELECTION CRITERIA:Trials in which individuals with pulmonary arteriovenous malformations were randomly allocated to embolisation compared to no treatment, surgical resection or embolisation using a different embolisation device. DATA COLLECTION AND ANALYSIS:Studies identified for potential inclusion were independently assessed for eligibility by two authors, with excluded studies further checked by a third author. No trials were identified for inclusion in the review and hence no analysis was performed. MAIN RESULTS:There were no randomised controlled trials included in the review; one ongoing trial has been identified which may be eligible for inclusion in the future. AUTHORS' CONCLUSIONS:There is no evidence from randomised controlled trials for embolisation of pulmonary arteriovenous malformations. However, randomised controlled trials are not always feasible on ethical grounds. Accumulated data from observational studies suggest that embolisation is a safe procedure which reduces morbidity and mortality. A standardised approach to reporting with long-term follow-up through registry studies can help to strengthen the evidence for embolisation in the absence of randomised controlled trials.

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Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation.

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