Epigenetic regulation of endothelial-cell-mediated vascular repair

FEBS Journal

Volumn 282, Issue 9, 2015, Pages 1605-1629

  Fraineau, Sylvain ^a,b,c   Palii, Carmen G ^a,c   Allan, David S ^a   Brand, Marjorie ^a,b,c  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

^c UNIVERSITY OF OTTAWA   (Canada)

Author keywords

DNA methylation; endothelial progenitors; epigenetic drugs; epigenetics; histone acetylation; histone methylation; non coding RNAs; stem cell therapy; transcription factors; vascular ischemic disease

Indexed keywords

CARDIOVASCULAR AGENT; DNA METHYLTRANSFERASE INHIBITOR; EZH2 INHIBITOR; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; LSD1 INHIBITOR; LYSINE; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; UNTRANSLATED RNA; HISTONE;

ARTICLE; BLOOD VESSEL INJURY; BLOOD VESSEL REACTIVITY; CELL FUNCTION; CELL LINEAGE; CELLS BY BODY ANATOMY; CEREBROVASCULAR ACCIDENT; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMATIN STRUCTURE; DEACETYLATION; DNA MODIFICATION; DRUG MECHANISM; ENDOTHELIUM CELL; ENZYME ACTIVITY; EPIGENETICS; GENETIC REGULATION; HEART INFARCTION; HISTONE ACETYLATION; HISTONE MODIFICATION; HUMAN; LIMB ISCHEMIA; MYELODYSPLASTIC SYNDROME; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROCESSING; REGULATORY MECHANISM; REVASCULARIZATION; STEM CELL; STEM CELL TRANSPLANTATION; TRANSCRIPTION REGULATION; BLOOD VESSEL; CYTOLOGY; DNA METHYLATION; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETIC TRANSCRIPTION; METABOLISM; VASCULAR ENDOTHELIUM;

BLOOD VESSELS; DNA METHYLATION; ENDOTHELIUM, VASCULAR; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HISTONES; HUMANS; STEM CELLS; TRANSCRIPTION, GENETIC;

EID: 84928490734     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/febs.13183     Document Type: Article

References (175)

1. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, &, Pellegrini G, (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363, 147-155.
2. Tsubota K, Satake Y, Kaido M, Shinozaki N, Shimmura S, Bissen-Miyajima H, &, Shimazaki J, (1999) Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med 340, 1697-1703.
3. Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, &, Lanza R, (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379, 713-720.
4. Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, Okita K, Osafune K, Arioka Y, Maeda T, et al.,. (2014) Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell 156, 663-677.
5. Fadini GP, Losordo D, &, Dimmeler S, (2012) Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res 110, 624-637.
6. Shantsila E, Watson T, &, Lip GY, (2007) Endothelial progenitor cells in cardiovascular disorders. J Am Coll Cardiol 49, 741-752.
7. Callum K, &, Bradbury A, (2000) ABC of arterial and venous disease: acute limb ischaemia. BMJ 320, 764-767.
8. Creager MA, Kaufman JA, &, Conte MS, (2012) Clinical practice. Acute limb ischemia. N Engl J Med 366, 2198-2206.
9. Leeper NJ, Hunter AL, &, Cooke JP, (2010) Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells. Circulation 122, 517-526.
10. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, &, Isner JM, (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964-967.
11. Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, Pollok K, Ferkowicz MJ, Gilley D, &, Yoder MC, (2004) Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 104, 2752-2760.
12. Lin Y, Weisdorf DJ, Solovey A, &, Hebbel RP, (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105, 71-77.
13. Medina RJ, O'Neill CL, Sweeney M, Guduric-Fuchs J, Gardiner TA, Simpson DA, &, Stitt AW, (2010) Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities. BMC Med Genomics 3, 18.
14. Critser PJ, &, Yoder MC, (2010) Endothelial colony-forming cell role in neoangiogenesis and tissue repair. Curr Opin Organ Transplant 15, 68-72.
15. Lee SH, Lee JH, Asahara T, Kim YS, Jeong HC, Ahn Y, Jung JS, &, Kwon SM, (2014) Genistein promotes endothelial colony-forming cell (ECFC) bioactivities and cardiac regeneration in myocardial infarction. PLoS One 9, e96155.
16. Bouvard C, Gafsou B, Dizier B, Galy-Fauroux I, Lokajczyk A, Boisson-Vidal C, Fischer AM, &, Helley D, (2010) alpha6-integrin subunit plays a major role in the proangiogenic properties of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 30, 1569-1575.
17. Saif J, Schwarz TM, Chau DY, Henstock J, Sami P, Leicht SF, Hermann PC, Alcala S, Mulero F, Shakesheff KM, et al.,. (2010) Combination of injectable multiple growth factor-releasing scaffolds and cell therapy as an advanced modality to enhance tissue neovascularization. Arterioscler Thromb Vasc Biol 30, 1897-1904.
18. Schwarz TM, Leicht SF, Radic T, Rodriguez-Araboalaza I, Hermann PC, Berger F, Saif J, Böcker W, Ellwart JW, Aicher A, et al.,. (2012) Vascular incorporation of endothelial colony-forming cells is essential for functional recovery of murine ischemic tissue following cell therapy. Arterioscler Thromb Vasc Biol 32, e13-e21.
19. Palii CG, Vulesevic B, Fraineau S, Pranckeviciene E, Griffith AJ, Chu A, Faralli H, Li Y, McNeill B, Sun J, et al.,. (2014) Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes. Cell Stem Cell 14, 644-657.
20. Moubarik C, Guillet B, Youssef B, Codaccioni JL, Piercecchi MD, Sabatier F, Lionel P, Dou L, Foucault-Bertaud A, Velly L, et al.,. (2011) Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem Cell Rev 7, 208-220.
21. Ward MR, Stewart DJ, &, Kutryk MJ, (2007) Endothelial progenitor cell therapy for the treatment of coronary disease, acute MI, and pulmonary arterial hypertension: current perspectives. Catheter Cardiovasc Interv 70, 983-998.
22. Medina RJ, O'Neill CL, Humphreys MW, Gardiner TA, &, Stitt AW, (2010) Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest Ophthalmol Vis Sci 51, 5906-5913.
23. Alphonse RS, Vadivel A, Fung M, Shelley WC, Critser PJ, Ionescu L, O'Reilly M, Ohls RK, McConaghy S, Eaton F, et al.,. (2014) Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth. Circulation 129, 2144-2157.
24. Marcelo KL, Goldie LC, &, Hirschi KK, (2013) Regulation of endothelial cell differentiation and specification. Circ Res 112, 1272-1287.
25. Park C, Kim TM, &, Malik AB, (2013) Transcriptional regulation of endothelial cell and vascular development. Circ Res 112, 1380-1400.
26. De Val S, &, Black BL, (2009) Transcriptional control of endothelial cell development. Dev Cell 16, 180-195.
27. Kubo H, &, Alitalo K, (2003) The bloody fate of endothelial stem cells. Genes Dev 17, 322-329.
28. De Val S, (2011) Key transcriptional regulators of early vascular development. Arterioscler Thromb Vasc Biol 31, 1469-1475.
29. Kume T, (2010) Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol Histopathol 25, 637-646.
30. Rössig L, Urbich C, Brühl T, Dernbach E, Heeschen C, Chavakis E, Sasaki K, Aicher D, Diehl F, Seeger F, et al.,. (2005) Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells. J Exp Med 201, 1825-1835.
31. Song Y, Li X, Wang D, Fu C, Zhu Z, Zou MH, &, Zhu Y, (2013) Transcription factor Krüppel-like factor 2 plays a vital role in endothelial colony forming cells differentiation. Cardiovasc Res 99, 514-524.
32. Li B, Carey M, &, Workman JL, (2007) The role of chromatin during transcription. Cell 128, 707-719.
33. Klose RJ, &, Zhang Y, (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8, 307-318.
34. Kouzarides T, (2007) Chromatin modifications and their function. Cell 128, 693-705.
35. Cedar H, &, Bergman Y, (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10, 295-304.
36. Rando OJ, &, Chang HY, (2009) Genome-wide views of chromatin structure. Annu Rev Biochem 78, 245-271.
37. Fish JE, Matouk CC, Rachlis A, Lin S, Tai SC, D'Abreo C, &, Marsden PA, (2005) The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem 280, 24824-24838.
38. Fish JE, &, Marsden PA, (2006) Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium. Cell Mol Life Sci 63, 144-162.
39. Fish JE, Yan MS, Matouk CC, St Bernard R, Ho JJ, Gavryushova A, Srivastava D, &, Marsden PA, (2010) Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones. J Biol Chem 285, 810-826.
40. Chan Y, Fish JE, D'Abreo C, Lin S, Robb GB, Teichert AM, Karantzoulis-Fegaras F, Keightley A, Steer BM, &, Marsden PA, (2004) The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J Biol Chem 279, 35087-35100.
41. Goretti E, Wagner DR, &, Devaux Y, (2013) Regulation of endothelial progenitor cell function by micrornas. Minerva Cardioangiol 61, 591-604.
42. Eken SM, Jin H, Chernogubova E, &, Maegdefessel L, (2013) Making sense in antisense: therapeutic potential of noncoding RNAs in diabetes-induced vascular dysfunction. J Diabetes Res 2013, 834727.
43. Laboratory of Cardiovascular Research, P. R. C.-H., Luxembourg, L.xembourg, Division of Cardiology, C. H., Luxembourg, L.xembourg, Luxembourg, L. o. C. R. P. R. C.-H. L. & Luxembourg, D. o. C. C. H. L. (2014) Role of microRNAs in endothelial progenitor cells: implication for cardiac repair. J Stem Cells 9, 107-115.
44. Meng S, Cao JT, Zhang B, Zhou Q, Shen CX, &, Wang CQ, (2012) Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol 53, 64-72.
45. Zhang J, Zhang Z, Zhang DY, Zhu J, Zhang T, &, Wang C, (2013) microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway. PLoS One 8, e83294.
46. Meng S, Cao J, Zhang X, Fan Y, Fang L, Wang C, Lv Z, Fu D, &, Li Y, (2013) Downregulation of microRNA-130a contributes to endothelial progenitor cell dysfunction in diabetic patients via its target Runx3. PLoS One 8, e68611.
47. Xu Q, Meng S, Liu B, Li MQ, Li Y, Fang L, &, Li YG, (2014) MicroRNA-130a regulates autophagy of endothelial progenitor cells through Runx3. Clin Exp Pharmacol Physiol 41, 351-357.
48. Zhu S, Deng S, Ma Q, Zhang T, Jia C, Zhuo D, Yang F, Wei J, Wang L, Dykxhoorn DM, et al.,. (2013) MicroRNA-10A∗ and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2. Circ Res 112, 152-164.
49. Chang TY, Huang TS, Wang HW, Chang SJ, Lo HH, Chiu YL, Wang YL, Hsiao CD, Tsai CH, Chan CH, et al.,. (2014) miRNome traits analysis on endothelial lineage cells discloses biomarker potential circulating microRNAs which affect progenitor activities. BMC Genom 15, 802.
50. Kaikkonen MU, Lam MT, &, Glass CK, (2011) Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res 90, 430-440.
51. Robb GB, Carson AR, Tai SC, Fish JE, Singh S, Yamada T, Scherer SW, Nakabayashi K, &, Marsden PA, (2004) Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript. J Biol Chem 279, 37982-37996.
52. Fish JE, Matouk CC, Yeboah E, Bevan SC, Khan M, Patil K, Ohh M, &, Marsden PA, (2007) Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase. J Biol Chem 282, 15652-15666.
53. Li K, Blum Y, Verma A, Liu Z, Pramanik K, Leigh NR, Chun CZ, Samant GV, Zhao B, Garnaas MK, et al.,. (2010) A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood 115, 133-139.
54. Yan MS, Matouk CC, &, Marsden PA, (2010) Epigenetics of the vascular endothelium. J Appl Physiol (1985) 109, 916-926.
55. Kohli RM, &, Zhang Y, (2013) TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472-479.
56. Banerjee S, &, Bacanamwo M, (2010) DNA methyltransferase inhibition induces mouse embryonic stem cell differentiation into endothelial cells. Exp Cell Res 316, 172-180.
57. Shirodkar AV, St Bernard R, Gavryushova A, Kop A, Knight BJ, Yan MS, Man HS, Sud M, Hebbel RP, Oettgen P, et al.,. (2013) A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing. Blood 121, 3531-3540.
58. Lagarkova MA, Volchkov PY, Philonenko ES, &, Kiselev SL, (2008) Efficient differentiation of hESCs into endothelial cells in vitro is secured by epigenetic changes. Cell Cycle 7, 2929-2935.
59. Lagarkova MA, Shutova MV, Bogomazova AN, Vassina EM, Glazov EA, Zhang P, Rizvanov AA, Chestkov IV, &, Kiselev SL, (2010) Induction of pluripotency in human endothelial cells resets epigenetic profile on genome scale. Cell Cycle 9, 937-946.
60. Ohtani K, Vlachojannis GJ, Koyanagi M, Boeckel JN, Urbich C, Farcas R, Bonig H, Marquez VE, Zeiher AM, &, Dimmeler S, (2011) Epigenetic regulation of endothelial lineage committed genes in pro-angiogenic hematopoietic and endothelial progenitor cells. Circ Res 109, 1219-1229.
61. Marks PA, &, Xu WS, (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107, 600-608.
62. Marks PA, (2010) Histone deacetylase inhibitors: a chemical genetics approach to understanding cellular functions. Biochim Biophys Acta 1799, 717-725.
63. Roth SY, Denu JM, &, Allis CD, (2001) Histone acetyltransferases. Annu Rev Biochem 70, 81-120.
64. Smith BC, &, Denu JM, (2009) Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 1789, 45-57.
65. Kuo MH, &, Allis CD, (1998) Roles of histone acetyltransferases and deacetylases in gene regulation. BioEssays 20, 615-626.
66. Gray SG, &, Ekström TJ, (2001) The human histone deacetylase family. Exp Cell Res 262, 75-83.
67. Guarani V, Deflorian G, Franco CA, Krüger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, et al.,. (2011) Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473, 234-238.
68. Potente M, &, Dimmeler S, (2008) Emerging roles of SIRT1 in vascular endothelial homeostasis. Cell Cycle 7, 2117-2122.
69. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, &, van Kuilenburg AB, (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370, 737-749.
70. Bolden JE, Peart MJ, &, Johnstone RW, (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5, 769-784.
71. Lf Chen, Fischle W, Verdin E, &, Greene WC, (2001) Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science 293, 1653-1657.
72. Crosson CE, Mani SK, Husain S, Alsarraf O, &, Menick DR, (2010) Inhibition of histone deacetylase protects the retina from ischemic injury. Invest Ophthalmol Vis Sci 51, 3639-3645.
73. Zhang Z, Qin X, Tong N, Zhao X, Gong Y, Shi Y, &, Wu X, (2012) Valproic acid-mediated neuroprotection in retinal ischemia injury via histone deacetylase inhibition and transcriptional activation. Exp Eye Res 94, 98-108.
74. Granger A, Abdullah I, Huebner F, Stout A, Wang T, Huebner T, Epstein JA, &, Gruber PJ, (2008) Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. FASEB J 22, 3549-3560.
75. Illi B, Scopece A, Nanni S, Farsetti A, Morgante L, Biglioli P, Capogrossi MC, &, Gaetano C, (2005) Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ Res 96, 501-508.
76. Chen W, Bacanamwo M, &, Harrison DG, (2008) Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription. J Biol Chem 283, 16293-16298.
77. Kaur H, Chen S, Xin X, Chiu J, Khan ZA, &, Chakrabarti S, (2006) Diabetes-induced extracellular matrix protein expression is mediated by transcription coactivator p300. Diabetes 55, 3104-3111.
78. Wei JQ, Shehadeh LA, Mitrani JM, Pessanha M, Slepak TI, Webster KA, &, Bishopric NH, (2008) Quantitative control of adaptive cardiac hypertrophy by acetyltransferase p300. Circulation 118, 934-946.
79. Shehadeh LA, Sharma S, Pessanha M, Wei JQ, Liu J, Yuan H, Rodrigues CO, Scherr M, Tsinoremas NF, &, Bishopric NH, (2013) MicroRNA-20a constrains p300-driven myocardial angiogenic transcription by direct targeting of p300. PLoS One 8, e79133.
80. Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, &, Livingston DM, (1996) An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci USA 93, 12969-12973.
81. Chiu JJ, &, Chien S, (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91, 327-387.
82. Hahn C, &, Schwartz MA, (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10, 53-62.
83. Chiu JJ, Usami S, &, Chien S, (2009) Vascular endothelial responses to altered shear stress: pathologic implications for atherosclerosis. Ann Med 41, 19-28.
84. Traub O, &, Berk BC, (1998) Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol 18, 677-685.
85. Lee DY, Lee CI, Lin TE, Lim SH, Zhou J, Tseng YC, Chien S, &, Chiu JJ, (2012) Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow. Proc Natl Acad Sci USA 109, 1967-1972.
86. Gan Y, Shen YH, Wang J, Wang X, Utama B, &, Wang XL, (2005) Role of histone deacetylation in cell-specific expression of endothelial nitric-oxide synthase. J Biol Chem 280, 16467-16475.
87. Hyndman KA, Ho DH, Sega MF, &, Pollock JS, (2014) Histone deacetylase 1 reduces NO production in endothelial cells via lysine deacetylation of NO synthase 3. Am J Physiol Heart Circ Physiol 307, 5.
88. Nishida K, Harrison DG, Navas JP, Fisher AA, Dockery SP, Uematsu M, Nerem RM, Alexander RW, &, Murphy TJ, (1992) Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest 90, 2092-2096.
89. Fleming I, &, Busse R, (1999) Signal transduction of eNOS activation. Cardiovasc Res 43, 532-541.
90. Zeng L, Zhang Y, Chien S, Liu X, &, Shyy JY, (2003) The role of p53 deacetylation in p21Waf1 regulation by laminar flow. J Biol Chem 278, 24594-24599.
91. Pandey D, Sikka G, Bergman Y, Kim JH, Ryoo S, Romer L, &, Berkowitz D, (2014) Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2. Arterioscler Thromb Vasc Biol 34, 1556-1566.
92. Fan J, Alsarraf O, Dahrouj M, Platt KA, Chou CJ, Rice DS, &, Crosson CE, (2013) Inhibition of HDAC2 protects the retina from ischemic injury. Invest Ophthalmol Vis Sci 54, 4072-4080.
93. Xiao Q, Zeng L, Zhang Z, Margariti A, Ali ZA, Channon KM, Xu Q, &, Hu Y, (2006) Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. Arterioscler Thromb Vasc Biol 26, 2244-2251.
94. Zeng L, Xiao Q, Margariti A, Zhang Z, Zampetaki A, Patel S, Capogrossi MC, Hu Y, &, Xu Q, (2006) HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. J Cell Biol 174, 1059-1069.
95. Zampetaki A, Zeng L, Margariti A, Xiao Q, Li H, Zhang Z, Pepe AE, Wang G, Habi O, deFalco E, et al.,. (2010) Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation 121, 132-142.
96. Zeng L, Wang G, Ummarino D, Margariti A, Xu Q, Xiao Q, Wang W, Zhang Z, Yin X, Mayr M, et al.,. (2013) Histone deacetylase 3 unconventional splicing mediates endothelial-to-mesenchymal transition through transforming growth factor β2. J Biol Chem 288, 31853-31866.
97. Chang S, McKinsey TA, Zhang CL, Richardson JA, Hill JA, &, Olson EN, (2004) Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol 24, 8467-8476.
98. Chang S, Young BD, Li S, Qi X, Richardson JA, &, Olson EN, (2006) Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell 126, 321-334.
99. Wang S, Li X, Parra M, Verdin E, Bassel-Duby R, &, Olson EN, (2008) Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7. Proc Natl Acad Sci USA 105, 7738-7743.
100. Sun X, Wei L, Chen Q, &, Terek RM, (2009) HDAC4 represses vascular endothelial growth factor expression in chondrosarcoma by modulating RUNX2 activity. J Biol Chem 284, 21881-21890.
101. Urbich C, Rössig L, Kaluza D, Potente M, Boeckel JN, Knau A, Diehl F, Geng JG, Hofmann WK, Zeiher AM, et al.,. (2009) HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood 113, 5669-5679.
102. Ha CH, Wang W, Jhun BS, Wong C, Hausser A, Pfizenmaier K, McKinsey TA, Olson EN, &, Jin ZG, (2008) Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem 283, 14590-14599.
103. Kwon IS, Wang W, Xu S, &, Jin ZG, (2014) Histone deacetylase 5 interacts with Krüppel-like factor 2 and inhibits its transcriptional activity in endothelium. Cardiovasc Res 104, 127-137.
104. Illi B, Dello Russo C, Colussi C, Rosati J, Pallaoro M, Spallotta F, Rotili D, Valente S, Ragone G, Martelli F, et al.,. (2008) Nitric oxide modulates chromatin folding in human endothelial cells via protein phosphatase 2A activation and class II histone deacetylases nuclear shuttling. Circ Res 102, 51-58.
105. Mottet D, Bellahcène A, Pirotte S, Waltregny D, Deroanne C, Lamour V, Lidereau R, &, Castronovo V, (2007) Histone deacetylase 7 silencing alters endothelial cell migration, a key step in angiogenesis. Circ Res 101, 1237-1246.
106. Turtoi A, Mottet D, Matheus N, Dumont B, Peixoto P, Hennequière V, Deroanne C, Colige A, De Pauw E, Bellahcène A, et al.,. (2012) The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells. Angiogenesis 15, 543-554.
107. Margariti A, Zampetaki A, Xiao Q, Zhou B, Karamariti E, Martin D, Yin X, Mayr M, Li H, Zhang Z, et al.,. (2010) Histone deacetylase 7 controls endothelial cell growth through modulation of beta-catenin. Circ Res 106, 1202-1211.
108. Margariti A, Xiao Q, Zampetaki A, Zhang Z, Li H, Martin D, Hu Y, Zeng L, &, Xu Q, (2009) Splicing of HDAC7 modulates the SRF-myocardin complex during stem-cell differentiation towards smooth muscle cells. J Cell Sci 122, 460-470.
109. Ha CH, Jhun BS, Kao HY, &, Jin ZG, (2008) VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating matrix metalloproteinase expression and angiogenesis. Arterioscler Thromb Vasc Biol 28, 1782-1788.
110. Yu D, Chen W, Ren J, Zhang T, Yang K, Wu G, &, Liu H, (2014) VEGF-PKD1-HDAC7 signaling promotes endothelial progenitor cell migration and tube formation. Microvasc Res 91, 66-72.
111. Kaluza D, Kroll J, Gesierich S, Manavski Y, Boeckel JN, Doebele C, Zelent A, Rössig L, Zeiher AM, Augustin HG, et al.,. (2013) Histone deacetylase 9 promotes angiogenesis by targeting the antiangiogenic microRNA-17-92 cluster in endothelial cells. Arterioscler Thromb Vasc Biol 33, 533-543.
112. Kaluza D, Kroll J, Gesierich S, Yao TP, Boon RA, Hergenreider E, Tjwa M, Rössig L, Seto E, Augustin HG, et al.,. (2011) Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacetylation of cortactin. EMBO J 30, 4142-4156.
113. Potente M, Ghaeni L, Baldessari D, Mostoslavsky R, Rossig L, Dequiedt F, Haendeler J, Mione M, Dejana E, Alt FW, et al.,. (2007) SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev 21, 2644-2658.
114. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, &, Irani K, (2007) SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA 104, 14855-14860.
115. Hou J, Chong ZZ, Shang YC, &, Maiese K, (2010) Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res 7, 95-112.
116. Zu Y, Liu L, Lee MY, Xu C, Liang Y, Man RY, Vanhoutte PM, &, Wang Y, (2010) SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circ Res 106, 1384-1393.
117. Vassallo PF, Simoncini S, Ligi I, Chateau AL, Bachelier R, Robert S, Morere J, Fernandez S, Guillet B, Marcelli M, et al.,. (2014) Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression. Blood 123, 2116-2126.
118. Cloos PA, Christensen J, Agger K, &, Helin K, (2008) Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22, 1115-1140.
119. Zhou VW, Goren A, &, Bernstein BE, (2011) Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet 12, 7-18.
120. Calo E, &, Wysocka J, (2013) Modification of enhancer chromatin: what, how, and why? Mol Cell 49, 825-837.
121. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, et al.,. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315-326.
122. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, &, Wysocka J, (2011) A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279-283.
123. Gifford CA, Ziller MJ, Gu H, Trapnell C, Donaghey J, Tsankov A, Shalek AK, Kelley DR, Shishkin AA, Issner R, et al.,. (2013) Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153, 1149-1163.
124. Voigt P, Tee WW, &, Reinberg D, (2013) A double take on bivalent promoters. Genes Dev 27, 1318-1338.
125. Varier RA, &, Timmers HT, (2011) Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta 1815, 75-89.
126. Eissenberg JC, &, Shilatifard A, (2010) Histone H3 lysine 4 (H3K4) methylation in development and differentiation. Dev Biol 339, 240-249.
127. Ernst P, &, Vakoc CR, (2012) WRAD: enabler of the SET1-family of H3K4 methyltransferases. Brief Funct Genomics 11, 217-226.
128. Ernst P, Mabon M, Davidson AJ, Zon LI, &, Korsmeyer SJ, (2004) An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr Biol 14, 2063-2069.
129. Ernst P, Fisher JK, Avery W, Wade S, Foy D, &, Korsmeyer SJ, (2004) Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell 6, 437-443.
130. Hess JL, Yu BD, Li B, Hanson R, &, Korsmeyer SJ, (1997) Defects in yolk sac hematopoiesis in Mll-null embryos. Blood 90, 1799-1806.
131. Diehl F, Rössig L, Zeiher AM, Dimmeler S, &, Urbich C, (2007) The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood 109, 1472-1478.
132. Li Q, Shi L, Gui B, Yu W, Wang J, Zhang D, Han X, Yao Z, &, Shang Y, (2011) Binding of the JmjC demethylase JARID1B to LSD1/NuRD suppresses angiogenesis and metastasis in breast cancer cells by repressing chemokine CCL14. Cancer Res 71, 6899-6908.
133. Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR, Reslan OM, Adler GK, Williams GH, Shi Y, et al.,. (2011) Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol 301, H1862-H1871.
134. Wang GG, Allis CD, &, Chi P, (2007) Chromatin remodeling and cancer. Part I: Covalent histone modifications. Trends Mol Med 13, 363-372.
135. Black JC, Van Rechem C, &, Whetstine JR, (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 48, 491-507.
136. Snowden AW, Gregory PD, Case CC, &, Pabo CO, (2002) Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr Biol 12, 2159-2166.
137. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, et al.,. (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624-629.
138. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, et al.,. (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100, 11606-11611.
139. Tonini T, D'Andrilli G, Fucito A, Gaspa L, &, Bagella L, (2008) Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements. J Cell Physiol 214, 295-300.
140. Richter GH, Plehm S, Fasan A, Rössler S, Unland R, Bennani-Baiti IM, Hotfilder M, Löwel D, von Luettichau I, Mossbrugger I, et al.,. (2009) EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci USA 106, 5324-5329.
141. Lu C, Han HD, Mangala LS, Ali-Fehmi R, Newton CS, Ozbun L, Armaiz-Pena GN, Hu W, Stone RL, Munkarah A, et al.,. (2010) Regulation of tumor angiogenesis by EZH2. Cancer Cell 18, 185-197.
142. Smits M, Mir SE, Nilsson RJ, van der Stoop PM, Niers JM, Marquez VE, Cloos J, Breakefield XO, Krichevsky AM, Noske DP, et al.,. (2011) Down-regulation of miR-101 in endothelial cells promotes blood vessel formation through reduced repression of EZH2. PLoS One 6, e16282.
143. Dreger H, Ludwig A, Weller A, Stangl V, Baumann G, Meiners S, &, Stangl K, (2012) Epigenetic regulation of cell adhesion and communication by enhancer of zeste homolog 2 in human endothelial cells. Hypertension 60, 1176-1183.
144. Mitic T, Caporali A, Floris I, Meloni M, Marchetti M, Urrutia R, Angelini GD, &, Emanueli C, (2015) EZH2 modulates angiogenesis in vitro and in a mouse model of limb ischemia. Mol Ther 23, 32-42.
145. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, et al.,. (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463, 360-363.
146. Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE, &, Helin K, (2007) UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449, 731-734.
147. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, et al.,. (2000) Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome Res 10, 1546-1560.
148. Hu M, Sun XJ, Zhang YL, Kuang Y, Hu CQ, Wu WL, Shen SH, Du TT, Li H, He F, et al.,. (2010) Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proc Natl Acad Sci USA 107, 2956-2961.
149. Khan C, Pathe N, Fazal S, Lister J, &, Rossetti JM, (2012) Azacitidine in the management of patients with myelodysplastic syndromes. Ther Adv Hematol 3, 355-373.
150. Derissen EJ, Beijnen JH, &, Schellens JH, (2013) Concise drug review: azacitidine and decitabine. Oncologist 18, 619-624.
151. Dhanak D, &, Jackson P, (2014) Development and classes of epigenetic drugs for cancer. Biochem Biophys Res Commun 455, 58-69.
152. Rafehi H, Balcerczyk A, Lunke S, Kaspi A, Ziemann M, Kn H, Okabe J, Khurana I, Ooi J, Khan AW, et al.,. (2014) Vascular histone deacetylation by pharmacological HDAC inhibition. Genome Res 24, 1271-1284.
153. Iordache F, Buzila C, Constantinescu A, Andrei E, &, Maniu H, (2012) Histone deacetylase (HDAC) inhibitors down-regulate endothelial lineage commitment of umbilical cord blood derived endothelial progenitor cells. Int J Mol Sci 13, 15074-15085.
154. Rössig L, Li H, Fisslthaler B, Urbich C, Fleming I, Förstermann U, Zeiher AM, &, Dimmeler S, (2002) Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis. Circ Res 91, 837-844.
155. Gan Y, Shen YH, Utama B, Wang J, Coselli J, &, Wang XL, (2006) Dual effects of histone deacetylase inhibition by trichostatin A on endothelial nitric oxide synthase expression in endothelial cells. Biochem Biophys Res Commun 340, 29-34.
156. Thaler F, &, Minucci S, (2011) Next generation histone deacetylase inhibitors: the answer to the search for optimized epigenetic therapies? Expert Opin Drug Discov 6, 393-404.
157. Ria R, Catacchio I, Berardi S, De Luisi A, Caivano A, Piccoli C, Ruggieri V, Frassanito MA, Ribatti D, Nico B, et al.,. (2014) HIF-1α of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target. Clin Cancer Res 20, 847-858.
158. Michaelis M, Michaelis UR, Fleming I, Suhan T, Cinatl J, Blaheta RA, Hoffmann K, Kotchetkov R, Busse R, &, Nau H, (2004) Valproic acid inhibits angiogenesis in vitro and in vivo. Mol Pharmacol 65, 520-527.
159. Michaelis M, Suhan T, Michaelis UR, Beek K, Rothweiler F, Tausch L, Werz O, Eikel D, Zörnig M, Nau H, et al.,. (2006) Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells. Cell Death Differ 13, 446-453.
160. Dokmanovic M, Clarke C, &, Marks PA, (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5, 981-989.
161. Lee MG, Wynder C, Schmidt DM, McCafferty DG, &, Shiekhattar R, (2006) Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol 13, 563-567.
162. Konovalov S, &, Garcia-Bassets I, (2013) Analysis of the levels of lysine-specific demethylase 1 (LSD1) mRNA in human ovarian tumors and the effects of chemical LSD1 inhibitors in ovarian cancer cell lines. J Ovarian Res 6, 75.
163. Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, et al.,. (2012) Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med 18, 605-611.
164. Shi L, Cui S, Engel JD, &, Tanabe O, (2013) Lysine-specific demethylase 1 is a therapeutic target for fetal hemoglobin induction. Nat Med 19, 291-294.
165. Glazer RI, Hartman KD, Knode MC, Richard MM, Chiang PK, Tseng CK, &, Marquez VE, (1986) 3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun 135, 688-694.
166. Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, Karuturi RK, Tan PB, Liu ET, &, Yu Q, (2007) Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 21, 1050-1063.
167. Miranda TB, Cortez CC, Yoo CB, Liang G, Abe M, Kelly TK, Marquez VE, &, Jones PA, (2009) DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 8, 1579-1588.
168. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A, Diaz E, et al.,. (2012) EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 492, 108-112.
169. Verma SK, Tian X, LaFrance LV, Duquenne C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA, et al.,. (2012) Identification of potent, selective, cell-active inhibitors of the histone lysine methyltransferase EZH2. ACS Med Chem Lett 3, 1091-1096.
170. Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J, et al.,. (2012) A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 8, 890-896.
171. Amatangelo MD, Garipov A, Li H, Conejo-Garcia JR, Speicher DW, &, Zhang R, (2013) Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition. Cell Cycle 12, 2113-2119.
172. Béguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, Rosen M, Shen H, Yang SN, Wang L, Ezponda T, et al.,. (2013) EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23, 677-692.
173. Mozzetta C, Pontis J, Fritsch L, Robin P, Portoso M, Proux C, Margueron R, &, Ait-Si-Ali S, (2014) The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing. Mol Cell 53, 277-289.
174. Han H, Yang X, Pandiyan K, &, Liang G, (2013) Synergistic re-activation of epigenetically silenced genes by combinatorial inhibition of DNMTs and LSD1 in cancer cells. PLoS One 8, e75136.
175. Fiskus W, Sharma S, Shah B, Portier BP, Devaraj SG, Liu K, Iyer SP, Bearss D, &, Bhalla KN, (2014) Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells. Leukemia 28, 2155-2164.