Vascular and Lymphatic Malformations: Perspectives From Human and Vertebrate Studies

Abstract

Vascular malformations, affecting ≈1% to 1.5% of the population, comprise a spectrum of developmental patterning defects of capillaries, arteries, veins, and/or lymphatics. The majority of vascular malformations occur sporadically; however, inherited malformations exist as a part of complex congenital diseases. The malformations, ranging from birthmarks to life-threatening conditions, are present at birth, but may reveal signs and symptoms-including pain, bleeding, disfigurement, and functional defects of vital organs-in infancy, childhood, or adulthood. Vascular malformations often exhibit recurrent patterns at affected sites due to the lack of curative treatments. This review series provides a state-of-the-art assessment of vascular malformation research at basic, clinical, genetic, and translational levels.

Keywords: arteries; capillaries; cell proliferation; hemangiomas; vascular malformation.

Figure

Hepatic endothelial gain-of-function KRAS^G12D or BRAFV^600E mutations cause cavernous vascular malformations via activation of KRAS-BRAF-MAP2K-MAPK1 signaling pathway. Contiguous expression of adherens junctional proteins in KRAS or BRAF mutant hepatic endothelium promote cavernous sinusoidal expansion instead of branching. Concurrent administration of Food and Drug Administration-approved dabrafenib and trametinib inhibits growth of BRAF^V600E-driven cavernous sinusoidal malformations. Adapted from Janardhan HP et al.