<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Theofilatos, D.</style></author><author><style face="normal" font="default" size="100%">Fotakis, P.</style></author><author><style face="normal" font="default" size="100%">Valanti, E.</style></author><author><style face="normal" font="default" size="100%">Sanoudou, D.</style></author><author><style face="normal" font="default" size="100%">Zannis, V.</style></author><author><style face="normal" font="default" size="100%">Kardassis, D.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">HDL-apoA-I induces the expression of angiopoietin like 4 (ANGPTL4) in endothelial cells via a PI3K/AKT/FOXO1 signaling pathway</style></title><secondary-title><style face="normal" font="default" size="100%">MetabolismMetabolismMetabolism</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Metabolism: clinical and experimental</style></alt-title><short-title><style face="normal" font="default" size="100%">Metabolism: clinical and experimentalMetabolism: clinical and experimental</style></short-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Angiopoietin-like 4 Protein/*biosynthesis/drug effects/genetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apolipoprotein A-I/*pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Endothelial Cells/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Forkhead Box Protein O1/drug effects/genetics/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression/drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Silencing</style></keyword><keyword><style  face="normal" font="default" size="100%">Healthy Volunteers</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipoproteins, HDL/*pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Transgenic</style></keyword><keyword><style  face="normal" font="default" size="100%">Microarray Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Oncogene Protein v-akt/drug effects/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphatidylinositol 3-Kinases/drug effects/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Transport/drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Small Interfering/pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction/*drug effects</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">87</style></volume><pages><style face="normal" font="default" size="100%">36-47</style></pages><isbn><style face="normal" font="default" size="100%">1532-8600 (Electronic)0026-0495 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">BACKGROUND: High Density Lipoprotein (HDL) and its main protein component, apolipoprotein A-I (apoA-I), have numerous atheroprotective functions on various tissues including the endothelium. Therapies based on reconstituted HDL containing apoA-I (rHDL-apoA-I) have been used successfully in patients with acute coronary syndrome, peripheral vascular disease or diabetes but very little is known about the genomic effects of rHDL-apoA-I and how they could contribute to atheroprotection. OBJECTIVE: The present study aimed to understand the endothelial signaling pathways and the genes that may contribute to rHDL-apoA-I-mediated atheroprotection. METHODS: Human aortic endothelial cells (HAECs) were treated with rHDL-apoA-I and their total RNA was analyzed with whole genome microarrays. Validation of microarray data was performed using multiplex RT-qPCR. The expression of ANGPTL4 in EA.hy926 endothelial cells was determined by RT-qPCR and Western blotting. The contribution of signaling kinases and transcription factors in ANGPTL4 gene regulation by HDL-apoA-I was assessed by RT-qPCR, Western blotting and immunofluorescence using chemical inhibitors or siRNA-mediated gene silencing. RESULTS: It was found that 410 transcripts were significantly changed in the presence of rHDL-apoA-I and that angiopoietin like 4 (ANGPTL4) was one of the most upregulated and biologically relevant molecules. In validation experiments rHDL-apoA-I, as well as natural HDL from human healthy donors or from transgenic mice overexpressing human apoA-I (TgHDL-apoA-I), increased ANGPTL4 mRNA and protein levels. ANGPTL4 gene induction by HDL was direct and was blocked in the presence of inhibitors for the AKT or the p38 MAP kinases. TgHDL-apoA-I caused phosphorylation of the transcription factor forkhead box O1 (FOXO1) and its translocation from the nucleus to the cytoplasm. Importantly, a FOXO1 inhibitor or a FOXO1-specific siRNA enhanced ANGPTL4 expression, whereas administration of TgHDL-apoA-I in the presence of the FOXO1 inhibitor or the FOXO1-specific siRNA did not induce further ANGPTL4 expression. These data suggest that FOXO1 functions as an inhibitor of ANGPTL4, while HDL-apoA-I blocks FOXO1 activity and induces ANGPTL4 through the activation of AKT. CONCLUSION: Our data provide novel insights into the global molecular effects of HDL-apoA-I on endothelial cells and identify ANGPTL4 as a putative mediator of the atheroprotective functions of HDL-apoA-I on the artery wall, with notable therapeutic potential.</style></abstract><accession-num><style face="normal" font="default" size="100%">29928895</style></accession-num><notes><style face="normal" font="default" size="100%">Theofilatos, DimitrisFotakis, PanagiotisValanti, EfiSanoudou, DespinaZannis, VassilisKardassis, DimitrisengResearch Support, Non-U.S. Gov't2018/06/22 06:00Metabolism. 2018 Oct;87:36-47. doi: 10.1016/j.metabol.2018.06.002. Epub 2018 Jun 18.</style></notes><auth-address><style face="normal" font="default" size="100%">Laboratory of Biochemistry, University of Crete School of Medicine, Heraklion, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Greece.Section of Molecular Genetics, Boston University Medical School, Boston, USA.4th Department of Internal Medicine, &quot;Attikon&quot; Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.Laboratory of Biochemistry, University of Crete School of Medicine, Heraklion, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Greece. Electronic address: kardasis@imbb.forth.gr.</style></auth-address></record></records></xml>