HDAC1: an environmental sensor regulating endothelial function.

Academic Article


  • The histone deacetylases (HDACs) are a family of enzymes that catalyze lysine deacetylation of both histone and non-histone proteins. Here we review, summarize, and provide perspectives on the literature regarding one such HDAC, HDAC1, in endothelial biology. In the endothelium, HDAC1 mediates the effects of external and environmental stimuli by regulating major endothelial functions such as angiogenesis, inflammatory signaling, redox homeostasis, and nitric oxide signaling. Angiogenesis is most often, but not exclusively, repressed by endothelial HDAC1. The regulation of inflammatory signaling is more complex as HDAC1 promotes or suppresses inflammatory signaling depending upon the environmental stimuli. HDAC1 is protective in models of atherosclerosis where loss of HDAC1 results in increased cytokine and cell adhesion molecule abundance. In other models, HDAC1 promotes inflammation by increasing cell adhesion molecules and repressing claudin-5 expression. Consistently, from many investigations, HDAC1 decreases antioxidant enzyme expression and nitric oxide production in the endothelium. HDAC1 decreases antioxidant enzyme expression through the deacetylation of histones and transcription factors, and also regulates nitric oxide production through regulating both the expression and activity of nitric oxide synthase 3. The HDAC1-dependent regulation of endothelial function through the deacetylation of both histone and non-histone proteins ultimately impacts whole animal physiology and health.
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  • Dunaway LS; Pollock JS