Int J Med Sci 2014; 11(9):955-961. doi:10.7150/ijms.9316
Cyclic Phosphatidic Acid Inhibits Alkyl-Glycerophosphate-Induced Downregulation of Histone Deacetylase 2 Expression and Suppresses the Inflammatory Response in Human Coronary Artery Endothelial Cells
1. Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan
2. Institue for Biomedical Sciences, Shinshu University Interdisciplinary Cluster for Cutting Edge Research 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
3. Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806, Japan
Activation of the endothelium by alkyl-glycerophosphate (AGP) has been implicated in the development of atherosclerosis. Our previous study suggested that cyclic phosphatidic acid (cPA) inhibits arterial wall remodeling in a rat model in vivo. However, the mechanisms through which specific target genes are regulated during this process remain unclear. Here, we examined whether cPA inhibited AGP-induced expression of class I histone deacetylases (HDACs, namely HDAC1, HDAC2, HDAC3, and HDAC8), which may affect subsequent transcriptional activity of target genes. Our experimental results showed that human coronary artery endothelial cells (HCAECs) expressed high levels of HDAC2 and low levels HDAC1, HDAC3, and HDAC8. Moreover, AGP treatment induced downregulation of HDAC2 expression in HCAECs. However, cotreatment with cPA inhibited this downregulation of HDAC2 expression. Interestingly, treatment with AGP increased the expression and secretion of endogenous interleukin (IL)-6 and IL-8; however, this effect was inhibited when HCAECs were cotreated with cPA or the synthetic peroxisome proliferator-activator receptor gamma (PPARγ) antagonist T0070907. Thus, our data suggested that cPA may have beneficial effects in inflammation-related cardiovascular disease by controlling HDAC2 regulation.
Keywords: Histone deacetylase, coronary artery endothelial cells, cyclic phosphatidic acid
Tsukahara T, Haniu H, Matsuda Y. Cyclic Phosphatidic Acid Inhibits Alkyl-Glycerophosphate-Induced Downregulation of Histone Deacetylase 2 Expression and Suppresses the Inflammatory Response in Human Coronary Artery Endothelial Cells. Int J Med Sci 2014; 11(9):955-961. doi:10.7150/ijms.9316. Available from http://www.medsci.org/v11p0955.htm