REVIEW ARTICLE Epigenetic regulation of endothelial-cell-mediated vascular repair Sylvain Fraineau1,2,3, Carmen G. Palii1,3, David S. Allan1 and Marjorie Brand1,2,3 1 Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada 2 Department of Cellular and Molecular Medicine, University of Ottawa, Canada 3 Ottawa Institute of Systems Biology, Canada Keywords Maintenance of vascular integrity is essential for the prevention of vascular DNA methylation; endothelial progenitors; disease and for recovery following cardiovascular, cerebrovascular and epigenetics; epigenetic drugs; histone peripheral vascular events including limb ischemia, heart attack and stroke. acetylation; histone methylation; non-coding Endothelial stem/progenitor cells have recently gained considerable interest RNAs; stem cell therapy; transcription factors; vascular ischemic disease due to their potential use in stem cell therapies to mediate revascularization after ischemic injury. Therefore, there is an urgent need to understand fun- Correspondence damental mechanisms regulating vascular repair in specific cell types to M. Brand, Sprott Center for Stem Cell develop new beneficial therapeutic interventions. In this review, we high- Research, Regenerative Medicine Program, light recent studies demonstrating that epigenetic mechanisms (including Ottawa Hospital Research Institute, Ottawa post-translational modifications of DNA and histones as well as non-cod- ON K1H8L6, Canada ing RNA-mediated processes) play essential roles in the regulation of endo- Fax: +1 613 739 6294 Tel: +1 613 737 7700 ext. 70336 thelial stem/progenitor cell functions through modifying chromatin E-mail:
[email protected] structure. Furthermore, we discuss the potential of using small molecules that modulate the activities of epigenetic enzymes to enhance the vascular (Received 21 October 2014, revised 17 repair function of endothelial cells and offer insight on potential strategies December 2014, accepted 19 December that may accelerate clinical applications.