Injectable chitosan hydrogel effectively controls lesion growth in a venous malformation murine model.

Purpose: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of chitosan hydrogel (CH) combined with sodium tetradecyl sulfate (STS) to sclerose and embolize venous malformations (VMs) by comparison with 3% STS foam and placebo in a mouse model.

Materials And Methods: Subcutaneous VMs were created by injecting HUVEC_TIE2-L914F cells, mixed with matrigel, into the back of athymic mice (Day [D] 0). After VM-like lesions were established at D10, 70 lesions were randomly assigned to one of six treatment groups (untreated, saline, 3% STS-foam, CH, 1% STS-CH, 3% STS-CH).

Trametinib as a promising therapeutic option in alleviating vascular defects in an endothelial KRAS-induced mouse model.

Somatic activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations have been reported in patients with arteriovenous malformations. By producing LSL-Kras (G12D); Cdh5 (PAC)-CreERT2 [iEC-Kras (G12D*)] mice, we hoped to activate KRAS within vascular endothelial cells (ECs) to generate an arteriovenous malformation mouse model. Neonatal mice were treated daily with tamoxifen from postnatal (PN) days 1-3.

Genetics of vascular anomalies.

Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The identification of genes mutated in the different malformations provides insight into the etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance. A few familial forms of vascular anomalies exist, but most cases occur sporadically.

Trauma Can Induce Telangiectases in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease of the fibrovascular tissue resulting in visceral vascular malformations and (muco-) cutaneous telangiectases with recurrent bleedings. The mechanism behind the disease is not fully understood; however, observations from HHT mouse models suggest that mechanical trauma may induce the formation of abnormal vessels. To assess the influence of environmental trauma (mechanical or light induced) on the number of telangiectases in patients with HHT, the number of telangiectases on the hands, face, and lips were counted on 103 HHT patients possessing at least three out of four Curaçao criteria.

A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using Ga-RGD PET/CT.

Arteriovenous malformations (AVMs) have an inherent capacity to form new blood vessels, resulting in excessive lesion growth, and this process is further triggered by the release of angiogenic factors. Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into the angiogenic status and treatment response of AVMs. This clinical feasibility study was performed to demonstrate that Ga-RGD PET/CT imaging can be used to quantitatively assess angiogenesis in peripheral AVMs.

Vascular Anomalies Caused by Abnormal Signaling within Endothelial Cells: Targets for Novel Therapies.

Vascular anomalies arise as a consequence of improper development and maintenance of the vasculature. Our knowledge on the pathophysiological bases of vascular anomalies has skyrocketed during the past 5 years. It is becoming clear that common intracellular signaling pathways are often activated by mutations, causing endothelial cell dysfunction.

GATA2 null mutation associated with incomplete penetrance in a family with Emberger syndrome.

Introduction: GATA2 mutations are associated with several conditions, including Emberger syndrome which is the association of primary lymphedema with hematological anomalies and an increased risk for myelodysplasia and leukemia.

Objective: To describe a family with Emberger syndrome with incomplete penetrance.

Methods: A DNA sequencing of GATA2 gene was performed in the parents and offspring (five individuals in total).

How to manage patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly inherited disorder of the fibrovascular tissue with a wide variety of clinical manifestations. Diagnosis is based on the clinical Curaçao criteria or molecular genetic testing. Dilated vessels can develop into telangiectases or larger vascular malformations in various organs, calling for an interdisciplinary approach.

Genetics of vascular malformations.

Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The majority of these occur sporadically, yet a few are reported to be familial. The identification of genes mutated in the different malformations provides insight into their etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance.

Common and distinctive pathogenetic features of arteriovenous malformations in hereditary hemorrhagic telangiectasia 1 and hereditary hemorrhagic telangiectasia 2 animal models--brief report.

Objective: Hereditary hemorrhagic telangiectasia is a genetic disorder characterized by visceral and mucocutaneous arteriovenous malformations (AVMs). Clinically indistinguishable hereditary hemorrhagic telangiectasia 1 and hereditary hemorrhagic telangiectasia 2 are caused by mutations in ENG and ALK1, respectively. In this study, we have compared the development of visceral and mucocutaneous AVMs in adult stages between Eng- and Alk1-inducible knockout (iKO) models.

Venous malformation-causative TIE2 mutations mediate an AKT-dependent decrease in PDGFB.

Mutations in the endothelial cell (EC) tyrosine kinase receptor TIE2 cause inherited and sporadic forms of venous malformation. The recurrent somatic mutation L914F and common germline mutation R849W differ in terms of phosphorylation level, as well as sub-cellular localization and trafficking of the receptor. Previous studies have shed light on certain pathogenic properties of R849W, but the mechanisms of action of L914F are unknown.

Physiological and genomic consequences of adrenergic deficiency during embryonic/fetal development in mice: impact on retinoic acid metabolism.

Adrenergic hormones are essential for early heart development. To gain insight into understanding how these hormones influence heart development, we evaluated genomic expression changes in embryonic hearts from adrenergic-deficient and wild-type control mice. To perform this study, we used a mouse model with targeted disruption of the Dopamine β-hydroxylase (Dbh) gene, whose product is responsible for enzymatic conversion of dopamine into norepinephrine.

TGF-β signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development.

The various organs of the body harbor blood vessel networks that display unique structural and functional features; however, the mechanisms that control organ-specific vascular development and physiology remain mostly unknown. In the developing mouse brain, αvβ8 integrin-mediated TGF-β activation and signaling is essential for normal blood vessel growth and sprouting. Whether integrins activate TGF-β signaling pathways in vascular endothelial cells (ECs), neural cells, or both, has yet to be determined.

Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques.

Despite rapid advances in the stem cell field, the ability to identify and track transplanted or migrating stem cells in vivo is limited. To overcome this limitation, we used magnetic resonance imaging (MRI) to detect and follow transplanted stem cells over a period of 28 days in mice using an established myocardial infarction model. Pluripotent mouse embryonic stem (mES) cells were expanded and induced to differentiate into beating cardiomyocytes in vitro.