Disorders of the Venous System

The vasculature is the first organ system to develop dur- ing embryogenesis, delivering nutrients, growth factors, and oxygen to tissues and removing waste products. It is therefore essential for development. The vascular sys- tem comprises four major compartments (arterial, capil- lary, and venous blood vessels, and lymphatic vessels), which have in common the presence of endothelial cells (ECs) forming the innermost layer. In blood vessels, the endothelial tubes are supported by a layer of vascular smooth muscle cells (vSMCs) and/or pericytes (together called mural cells) of variable thickness, whereas only a few SMCs are present in certain areas of large lymphatic vessels. The mechanisms that give rise to the mature vascular network are complex. These developmental processes, termed vasculogenesis, angiogenesis, and lymphangio- genesis, involve a plethora of signaling molecules and their receptors at various time-points. The best known are the angiopoietins (ANGPTs), ephrins, fibroblast growth factors, platelet-derived growth factor, trans- forming growth factor beta (TGFβ), and vascular endothelial growth factors. As suggested by numerous murine models showing abnormal vascular develop- ment, many other factors, including those participating in cell–cell and cell–matrix interactions, are probably also involved. Vascular anomalies result from localized defects that occur during vascular development (1,2). They are sub- divided into vascular tumors (mainly hemangiomas) and vascular malformations, which in turn are subcatego- rized according to the type(s) of vessel(s) altered (3,4). Thus, capillary, venous, arteriovenous, lymphatic, and combined malformations can be distinguished.