Panobinostat, a histone deacetylase inhibitor, rescues the angiogenic potential of endothelial colony-forming cells in moyamoya disease

• Published in: Child's nervous system Vol. 35; no. 5; pp. 823 - 831
• Main Authors: Jangra, Anshika, Choi, Seung Ah, Koh, Eun Jung, Moon, Youn Joo, Wang, Kyu-Chang, Phi, Ji Hoon, Lee, Ji Yeoun, Kim, Seung-Ki
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019
• Subjects: Medicine; Medicine & Public Health; Neurosciences; Neurosurgery; Original Article; HDAC inhibitor; Endothelial colony-forming cells; Moyamoya disease
• ISSN: 0256-7040; 1433-0350
• DOI: 10.1007/s00381-019-04099-y

Purpose Moyamoya disease (MMD) is one of the most common causes of pediatric stroke. We found defective angiogenic function and downregulation of retinaldehyde dehydrogenase 2 (RALDH2) in MMD endothelial colony-forming cells (ECFCs). Downregulation of RALDH2 mRNA was caused by decreased binding of acetyl-histone H3 (Ac-H3) to the RALDH2 promoter. In this study, we evaluated the feasibility of using a histone deacetylase (HDAC) inhibitor, panobinostat, to upregulate RALDH2 expression and restore the angiogenic potential of MMD ECFCs. Methods ECFCs from healthy normal controls and patients with MMD were isolated and characterized. After panobinostat treatment, western blot, tube formation, and chromatin immunoprecipitation (ChIP) assays were conducted in vitro. A matrigel plug assay was performed in vivo. Results Panobinostat increased the levels of Ac-H3 and Ac-H4 in both normal and MMD ECFCs but was much more effective in MMD ECFCs. Increased expression of RALDH2 by panobinostat was observed only in MMD ECFCs. Panobinostat increased the tube formation of both normal and MMD ECFCs in vitro and in vivo, but the effect was greater with MMD ECFCs. Conclusions We demonstrated that panobinostat increases the angiogenic ability of MMD ECFCs by regulating RALDH2 acetylation. Our results suggest that panobinostat might be a potent therapeutic option for MMD patients.