<?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%">Gkolfinopoulou, C.</style></author><author><style face="normal" font="default" size="100%">Soukou, F.</style></author><author><style face="normal" font="default" size="100%">Dafnis, I.</style></author><author><style face="normal" font="default" size="100%">Kellici, T.F.</style></author><author><style face="normal" font="default" size="100%">Sanoudou, D.</style></author><author><style face="normal" font="default" size="100%">Mavromoustakos, T.</style></author><author><style face="normal" font="default" size="100%">Stratikos,E.</style></author><author><style face="normal" font="default" size="100%">Chroni, A.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Structure-function analysis of naturally occurring apolipoprotein A-I L144R, A164S and L178P mutants provides insight on their role on HDL levels and cardiovascular risk</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Mol Life SciCell Mol Life SciCell Mol Life Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cellular and molecular life sciences : CMLS</style></alt-title><short-title><style face="normal" font="default" size="100%">Cellular and molecular life sciences : CMLSCellular and molecular life sciences : CMLS</style></short-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Apolipoprotein A-I/*genetics/metabolism/ultrastructure</style></keyword><keyword><style  face="normal" font="default" size="100%">ATP Binding Cassette Transporter, Subfamily G, Member 1/*genetics/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiovascular Diseases/*genetics/pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Movement/genetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Cholesterol, HDL/*genetics/metabolism/ultrastructure</style></keyword><keyword><style  face="normal" font="default" size="100%">Endothelial Cells/metabolism/pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Disease Risk Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Ketocholesterols/genetics/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Lipoproteins, HDL/genetics/metabolism/ultrastructure</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutant Proteins/genetics/metabolism/ultrastructure</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation/genetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Scavenger Receptors, Class E/genetics/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword><keyword><style  face="normal" font="default" size="100%">thermodynamics</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Feb</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">4</style></number><volume><style face="normal" font="default" size="100%">78</style></volume><pages><style face="normal" font="default" size="100%">1523-1544</style></pages><isbn><style face="normal" font="default" size="100%">1420-9071 (Electronic)1420-682X (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Naturally occurring point mutations in apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), may affect plasma HDL-cholesterol levels and cardiovascular risk. Here, we evaluated the effect of human apoA-I mutations L144R (associated with low HDL-cholesterol), L178P (associated with low HDL-cholesterol and increased cardiovascular risk) and A164S (associated with increased cardiovascular risk and mortality without low HDL-cholesterol) on the structural integrity and functions of lipid-free and lipoprotein-associated apoA-I in an effort to explain the phenotypes of subjects carrying these mutations. All three mutants, in lipid-free form, presented structural and thermodynamic aberrations, with apoA-I[L178P] presenting the greatest thermodynamic destabilization. Additionally, apoA-I[L178P] displayed reduced ABCA1-mediated cholesterol efflux capacity. When in reconstituted HDL (rHDL), apoA-I[L144R] and apoA-I[L178P] were more thermodynamically destabilized compared to wild-type apoA-I, both displayed reduced SR-BI-mediated cholesterol efflux capacity and apoA-I[L144R] showed severe LCAT activation defect. ApoA-I[A164S] was thermodynamically unaffected when in rHDL, but exhibited a series of functional defects. Specifically, it had reduced ABCG1-mediated cholesterol and 7-ketocholesterol efflux capacity, failed to reduce ROS formation in endothelial cells and had reduced capacity to induce endothelial cell migration. Mechanistically, the latter was due to decreased capacity of rHDL-apoA-I[A164S] to activate Akt kinase possibly by interacting with endothelial LOX-1 receptor. The impaired capacity of rHDL-apoA-I[A164S] to preserve endothelial function may be related to the increased cardiovascular risk for this mutation. Overall, our structure-function analysis of L144R, A164S and L178P apoA-I mutants provides insights on how HDL-cholesterol levels and/or atheroprotective properties of apoA-I/HDL are impaired in carriers of these mutations.</style></abstract><accession-num><style face="normal" font="default" size="100%">32666307</style></accession-num><notes><style face="normal" font="default" size="100%">Gkolfinopoulou, ChristinaSoukou, FayeDafnis, IoannisKellici, Tahsin FSanoudou, DespinaMavromoustakos, ThomasStratikos, EfstratiosChroni, AngelikiengMIS 5002691/Operational Programme &quot;Competitiveness, Entrepreneurship and Innovation&quot; (NSRF 2014-2020)MIS 5002550/Operational Programme &quot;Competitiveness, Entrepreneurship and Innovation&quot; (NSRF 2014-2020)MIS 5002755/Operational Programme &quot;Competitiveness, Entrepreneurship and Innovation&quot;Switzerland2020/07/16 06:00Cell Mol Life Sci. 2021 Feb;78(4):1523-1544. doi: 10.1007/s00018-020-03583-y. Epub 2020 Jul 14.</style></notes><auth-address><style face="normal" font="default" size="100%">Institute of Biosciences and Applications, National Center for Scientific Research &quot;Demokritos&quot;, Agia Paraskevi, 15341, Athens, Greece.Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, Athens, Greece.4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, 'Attikon' Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.Protein Chemistry Laboratory, Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Center for Scientific Research &quot;Demokritos&quot;, Agia Paraskevi, Athens, Greece.Institute of Biosciences and Applications, National Center for Scientific Research &quot;Demokritos&quot;, Agia Paraskevi, 15341, Athens, Greece. achroni@bio.demokritos.gr.</style></auth-address></record></records></xml>