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

• DOI: 10.1161/atvbaha.108.172528
• Publication Date: 2008-07-11T01:32:19Z
• Authors: Chang Hoon Ha; Bong Sook Jhun; Hung-Ying Kao; Zheng-Gen Jin
• Keywords: Fibulin

Histone acetylation/deacetylation plays an important role in the control of gene expression, tissue growth, and development. In particular, histone deacetylases 7 (HDAC7), a member class IIa HDACs, is crucial maintaining vascular integrity. However, whether HDAC7 involved processes endothelial signaling angiogenesis remains unclear. Here, we investigated growth factor (VEGF) angiogenesis.We show for first time that VEGF stimulated phosphorylation at sites Ser178, Ser344, Ser479 dose- time-dependent manner, which leads to cytoplasmic accumulation HDAC7. Using pharmacological inhibitors, siRNA, adenoviruses carrying dominant-negative mutants, found phospholipase Cgamma/protein kinase C/protein D1 (PKD1)-dependent signal pathway mediated by VEGF. Infection ECs with encoding mutant specifically deficient PKD1-dependent inhibited VEGF-induced angiogenic including matrix metalloproteinases MT1-matrix metalloproteinase (MMP) MMP10. Moreover, its targeting genes were VEGF-stimulated cell migration, tube formation, microvessel sprouting.Our results demonstrate stimulates cells modulating expression angiogenesis.