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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1689.)
© 2008 American Heart Association, Inc.

Editorials

A New Kid on the Block

PKD1: A Promising Target for Antiangiogenic Therapy?

Joachim Altschmied; Judith Haendeler

From the Institut fuer umweltmedizinische Forschung at the University of Duesseldorf GmbH, Germany.

An extract of the first 250 words of the full text is provided, because this article has no 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 C (PLC), 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.⁴ Class II HDACs appear to be dedicated to the control of tissue growth and development. Specifically, the class II enzyme HDAC7 is expressed exclusively in endothelial cells. Its disruption results in embryonic lethality by embryonic day 11 because of cardiovascular defects.⁵ Recently it has been shown that HDAC7 is critically involved in endothelial cell migration.⁶ However, the connection between VEGF, its target genes, and HDAC7 had not been uncovered until recently.

In this context, Ha et al, . . . [Full Text of this Article]

Related Article:

VEGF Stimulates HDAC7 Phosphorylation and Cytoplasmic Accumulation Modulating Matrix Metalloproteinase Expression and Angiogenesis

Chang Hoon Ha, Bong Sook Jhun, Hung-Ying Kao, and Zheng-Gen Jin
Arterioscler Thromb Vasc Biol 2008 28: 1782-1788. [Abstract] [Full Text] [PDF]