Abstract
Vascular malformations are developmental congenital abnormalities of the vascular system which may involve any segment of the vascular tree such as capillaries, veins, arteries, or lymphatics. Arteriovenous malformations (AVMs) are congenital vascular lesions, initially described as “erectile tumors,” characterized by atypical aggregation of dilated arteries and veins. They may occur in any part of the body, including the brain, heart, liver, and skin. Severe clinical manifestations occur only in the brain. There is absence of normal vascular structure at the subarteriolar level and dearth of capillary bed resulting in aberrant arteriovenous shunting. The causative factor and pathogenic mechanisms of AVMs are unknown. Importantly, no marker proteins have been identified for AVM. AVM is a high flow vascular malformation and is considered to develop because of variability in the hemodynamic forces of blood flow. Altered local hemodynamics in the blood vessels can affect cellular metabolism and may trigger epigenetic factors of the endothelial cell. The genes that are recognized to be associated with AVM might be modulated by various epigenetic factors. We propose that AVMs result from a series of changes in the DNA methylation and histone modifications in the genes connected to vascular development. Aberrant epigenetic modifications in the genome of endothelial cells may drive the artery or vein to an aberrant phenotype. This review focuses on the molecular pathways of arterial and venous development and discusses the role of hemodynamic forces in the development of AVM and possible link between hemodynamic forces and epigenetic mechanisms in the pathogenesis of AVM.
Highlights
International Society for the Study of Vascular Anomalies (ISSVA) has categorized vascular anomalies into two primary biological categories: (1) vascular neoplasms and (2) vascular malformations [1]
Arteriovenous malformations are congenital developmental disorders seen at many sites in the body
The possibility of combinatorial changes at genetic and epigenetic levels in vascular development may lead to the abnormal phenotype of Arteriovenous malformations (AVMs)
Summary
International Society for the Study of Vascular Anomalies (ISSVA) has categorized vascular anomalies into two primary biological categories: (1) vascular neoplasms and (2) vascular malformations [1]. Recent advances in vascular and molecular biology have identified that hemodynamic forces as well as genetic factors have significant roles in determining the fate of an endothelial cell, either of an artery or a vein. A detailed enquiry is warranted for analysis of methylation at H3 tail at K4, K9, K36, and H4 tail K20 positions in endothelial cells under various hemodynamics conditions Methylation at these positions largely influences the gene activity, and we hypothesize that hemodynamic blood flow could affect these methylation marks and alter the epigenetic landscape and chromatin structure in developing blood vessels. These mechanisms could be involved in the pathogenesis of AVM (Fig. 2). The role of any other epigenetic modifications and enzymes in the regulation of early and late phases of vascular development is currently unknown, and further studies are required to understand such epigenetic mechanisms in AVM development
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