A New Kid on the Block

Abstract

The formation of blood vessels through the process of angiogenesis is critical in normal vascular development and numerous vascular disorders. The most prominent stimulus for angiogenic processes in endothelial cells is vascular endothelial growth factor (VEGF), which regulates their migration, proliferation, and survival.1 The crucial role for this factor is documented by the lethal phenotype resulting from disruption of a single allele in mice.2,3 Binding of VEGF to its receptors activates several intracellular signaling molecules, among them phospholipase Cγ (PLCγ), protein kinase C (PKC), protein kinase D (PKD), and phosphatidyl-insitol-3 kinase (PI3K).1 The VEF-induced signaling events finally culminate in gene expression changes in the nucleus. See accompanying article on page 1782 A key regulator of gene expression is chromatin structure, which is largely determined by the acetylation status of histones. In general, acetylation of these nucleosomal proteins by histone acetyl transferases (HATs) stimulates transcription, whereas deacetylation by histone deacetylases (HDACs) leads to transcriptional repression. The HDAC family comprises 18 members in humans, which are classified based on their homologies to yeast proteins. …