Understanding Abnormalities in Vascular Specification and Remodeling

Abstract

Accurate classification, diagnosis, management, and treatment of vascular lesions in children can be hindered by the wide range of clinical presentations and varying clinical course of these lesions. In this issue of Pediatrics , Marler et al1 report novel findings that elevated levels of angiogenesis-related proteins, specifically high molecular weight matrix metalloproteinases (MMPs) and basic fibroblast growth factor (bFGF), can be detected in the urine of children with vascular anomalies and can mark clinical progression of these lesions. These findings suggest that a noninvasive test can be developed to characterize aggressive vascular malformations and tumors and provide additional evidence that antiangiogenic agents may be useful for the treatment of these lesions. To approach diagnosis and management of congenital vascular lesions rationally, an understanding of the basic cellular, molecular, and genetic mechanisms of blood vessel formation is required. Recent advances in the field of vascular biology have contributed to our knowledge of how blood vessels are assembled during early embryonic development. Blood vessel morphogenesis involves discrete steps in continuum that are regulated by specific signaling pathways involving soluble effectors, cytokines and their receptors, proteases, and extracellular matrix (ECM) components. These various pathways control integral events that contribute to the formation of a functional vasculature including endothelial and mural cell (pericyte/smooth muscle cell) differentiation, cell proliferation and migration, and the specification of arterial, venous, and lymphatic fate. Dysregulation of these processes can result in vascular malformations affecting 1 or multiple vascular types including capillary, arterial, venous, lymphatic, or arteriovenous channels. During embryonic development, blood vessels form de novo from endothelial progenitors by the process of vasculogenesis.2 This process has been studied most extensively in the mouse yolk sac, wherein endothelial progenitors are specified in the mesoderm and induced to form an initial capillary plexus by effectors derived from the adjacent … Address correspondence to Josephine M. Enciso, MD, Department of Pediatrics, Texas Children’s Hospital, Feigin Center, 6621 Fannin, FC 530.01, Houston, TX 77030. E-mail: jenciso{at}bcm.edu