Hereditary Vascular Anomalies

Abstract

Abstract-Increased understanding of the mechanisms of angiogenesis and lymphangiogenesis has provided a glimpse at some of the molecules involved in the pathophysiology of hemangiomas and vascular malformations. This review focuses on recent advances in our understanding of the mechanisms of angiogenesis/lymphangiogenesis and the differentiation of arterial, venous, and lymphatic vessels. We integrate this knowledge with new data obtained from genetic studies in humans, which have revealed a number of heretofore-unsuspected candidates involved in the development of familial vascular anomalies. We present a common infantile vascular tumor, hemangioma, and then focus on hereditary familial vascular and lymphatic malformations. We also summarize transgenic mouse models for some of these malformations. It seems reasonable to believe that novel therapeutic strategies will soon emerge for the treatment of hemangiomas and vascular malformations.

Expression of Growth Factors in Endotheliocytes in Vascular Malformations

“…Although the initial stages of mesodermal precursor cell differentiation into endotheliocytes run a normal course in the absence of TGF-β expression, the subsequent development of these cells with the formation of capillary-like tubules leads to the formation of abnormal vessels with defective walls. The absence of TGF-β-2 receptor in mice leads to development of similar abnormalities, which fact also proves the important role of the TGF-β -TGF-β receptor system in the formation of the integral vascular wall [13,15].…”

“…During the early embryogenesis the expression of TGF-β is characteristic of many tissues, including endothelial and hemopoietic precursor cells. Inactivation of TGF-β 1 in mouse embryos leads to their death (in 50% heterozygotes and 25% homozygotes) at early stages of gestation [13]. Disorders in the vascularization and hemopoiesis of the yolk sac are directly responsible for the death of these embryos.…”

“…Activation of VEGFR-2 stimulates the endotheliocyte proliferation and migration and increases the blood vessel permeability. The absence of VEGFR-3 gene causes embryonal death during early periods of gestation as a result of deficiency in the primary vascular network remodeling, which results in impossibility of normal development of the cardiovascular system before the formation of the lymph vessels [13].…”

“…Despite numerous recent studies of molecular mechanisms of angiogenesis [13], the role of the key angiogenic cytokines and growth factors and their interactions in the development of some malformations remains little studied. For example, the mediator interactions in arteriovenous, venous, and mixed angiodysplasias is an interesting problem.…”

Ultrastructural Characteristics of Peripheral Arteriovenous and Venous Angiodysplasias

“…One more manifestation of disorders in the vasculogenesis and angiogenesis processes of different nature is imbalance of the so-called accessory components of the vascular wall, seen from a lesser count or complete absence of pericytes in its structure [5]. Shortage of these cells, whose function is to stabilize the structure of the vascular wall and, presumably, phagocytosis, is essential for the pathogenesis of some angiodysplasias [9]. No pericytes were detected in the walls of the cavernous malformations in CNS [4].…”