The pathobiology of vascular malformations: insights from human and model organism genetics

Abstract

Vascular malformations may arise in any of the vascular beds present in the human body. These lesions vary in location, type, and clinical severity of the phenotype. In recent years, the genetic basis of several vascular malformations has been elucidated. This review will consider how the identification of the genetic factors contributing to different vascular malformations, with subsequent functional studies in animal models, has provided a better understanding of these factors that maintain vascular integrity in vascular beds, as well as their role in the pathogenesis of vascular malformations.

Comprehensive transcriptome analysis of cerebral cavernous malformation across multiple species and genotypes

“…The loss of all 3 known CCM genes in endothelium is embryonically lethal in mammals (12,20), hence highlighting the fundamental biological role of these genes and associated networks and pathways. We here cross-compared the transcriptomic profiles of human resected lesional NVUs, and 2 genotypes, Ccm1/Krit1 and Ccm3/Pdcd10, in both mouse BMECs and C. elegans.…”

“…A mutation of GNAO1 has been shown to promote cellular transformation and oncogenic signaling (18). Similarly, a mutation in GNAQ, a G αq protein-coding gene, has been reported to cause constitutive subunit activation by attenuating GTPase activity of the α subunit (20). A greater number of ECs with mutations on GNAQ has been shown to be associated with neurovascular disorders, including capillary malformations, Sturge-Weber syndrome, as well as port-wine stains (21,22).…”

Arterial Tortuosity Syndrome in a Neonate

“…The pathophysiological features of ATS include compromised vascular integrity in the arterial vascular beds and disorganized connective tissues overlying blood vessels and even nonvas cu lar structures throughout the body leading to increased flexi bility and reduced strength of the vessel wall and other con nec tive tissues 9) . The gene causing ATS is SLC2A10, encoding glucose transporter type 10 (GLUT10), located at chromosome .…”

“…The gene causing ATS is SLC2A10, encoding glucose transporter type 10 (GLUT10), located at chromosome . Recessive lossoffunction mutations of the SLC2A10 gene lead to disinhibition of the transforming growth factor beta signaling pathway and inhibition of proper extracellular matrix formation causing compromised vascular integrity and disorganized con nective tissues 2,9) . Expression of the SLC2A10 gene has been identified in several tissues, and high levels of SLC2A10 gene expression have been noted in the aortic vascular smooth mus cle cells 9,10) .…”

EOFAZ inhibits endothelial‑to‑mesenchymal transition through downregulation of KLF4

“…β-actin was used as the loading control. different types of cancer(42), myocardial infarction(43), cerebral cavernous malformations(44), vascular remolding and different types of organ fibrosis(40,41). during this process, TGF-β1 activates EndMT via multiple pathways…”