Research Topics
Genomes and Genes | Vassilis ZannisSummaryAffiliation: Boston University Country: USA Publications
Research Grants
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Publications
Transcriptional regulation of the human apolipoprotein genesV I Zannis
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 239, USA
Front Biosci 6:D456-504. 2001..Understanding the transcriptional regulatory mechanism of the apolipoprotein genes may allow, in the long run, selective increase of anti-atherogenic lipoproteins and thus reduce the risk of cardiovascular disease...- Discrete roles of apoA-I and apoE in the biogenesis of HDL species: lessons learned from gene transfer studies in different mouse modelsVassilis I Zannis
Molecular Genetics, Whitaker Cardiovascular Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, Boston, MA 02118 2394, USA
Ann Med 40:14-28. 2008..The apoE-containing HDL particles formed in the circulation may have atheroprotective properties. ApoE-containing HDL may also have important biological functions in the brain that confer protection from Alzheimer's disease... - Regulatory gene mutations affecting apolipoprotein gene expression: functions and regulatory behavior of known genes may guide future pharmacogenomic approaches to therapyVassilis I Zannis
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA
Clin Chem Lab Med 41:411-24. 2003.... - Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDLVassilis I Zannis
Molecular Genetics, Whitaker Cardiovascular Institute and Department of Biochemistry, Boston University School of Medicine, MA 02118, USA
J Mol Med (Berl) 84:276-94. 2006.... - Transcriptional regulatory mechanisms of the human apolipoprotein genes in vitro and in vivoV I Zannis
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 2394, USA
Curr Opin Lipidol 12:181-207. 2001..This may have beneficial effects and may confer protection from atherosclerosis to humans... - The central helices of ApoA-I can promote ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux. Amino acid residues 220-231 of the wild-type ApoA-I are required for lipid efflux in vitro and high density lipoprotein formation in vivoAngeliki Chroni
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 278:6719-30. 2003.... - Substitutions of glutamate 110 and 111 in the middle helix 4 of human apolipoprotein A-I (apoA-I) by alanine affect the structure and in vitro functions of apoA-I and induce severe hypertriglyceridemia in apoA-I-deficient miceAngeliki Chroni
Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Massachusetts, USA
Biochemistry 43:10442-57. 2004..The findings indicate that subtle structural alterations in apoA-I may alter the stability and functions of apoA-I and high-density lipoprotein (HDL) and may cause hypertriglyceridemia... 
Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the participation of ABCA1 and LCATKyriakos E Kypreos
Molecular Genetics, Whitaker Cardiovascular Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, 715 Albany Street W509, Boston, MA 02118, USA
Biochem J 403:359-67. 2007..HDL particles generated by this pathway may account at least for some of the atheroprotective functions of apoE...- Lipid-free structure and stability of apolipoprotein A-I: probing the central region by mutationIrina N Gorshkova
Department of Physiology and Biophysics and Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA
Biochemistry 41:10529-39. 2002.... - Naturally occurring and bioengineered apoA-I mutations that inhibit the conversion of discoidal to spherical HDL: the abnormal HDL phenotypes can be corrected by treatment with LCATGeorgios Koukos
Molecular Genetics, Departmental of Medicine and Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA
Biochem J 406:167-74. 2007..The correction of the aberrant HDL phenotypes by treatment with LCAT suggests a potential therapeutic intervention for HDL abnormalities that result from specific mutations in apoA-I... - Domains of apoE required for binding to apoE receptor 2 and to phospholipids: implications for the functions of apoE in the brainXiaoping Li
Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 42:10406-17. 2003..3 microg/mL). The findings establish that the apoER2 binding domain of apoE is in the 1-165 amino terminal region, whereas the carboxy terminal 230-299 region of apoE is required for efficient initial association with phospholipids... - Deletions of helices 2 and 3 of human apoA-I are associated with severe dyslipidemia following adenovirus-mediated gene transfer in apoA-I-deficient miceAngeliki Chroni
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 44:4108-17. 2005..We conclude that alterations in apoA-I not only may have adverse effects on HDL biosynthesis but also may promote dyslipidemia due to interference of the apoA-I mutants on the overall cholesterol and triglycerides homeostasis... - Reconstituted discoidal ApoE-phospholipid particles are ligands for the scavenger receptor BI. The amino-terminal 1-165 domain of ApoE suffices for receptor bindingXiaoping Li
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 277:21149-57. 2002..SR-BI-apoE interactions may contribute to cholesterol homeostasis in tissues and cells expressing SR-BI that are accessible to apoE-containing lipoproteins... - Generation of a recombinant apolipoprotein E variant with improved biological functions: hydrophobic residues (LEU-261, TRP-264, PHE-265, LEU-268, VAL-269) of apoE can account for the apoE-induced hypertriglyceridemiaKyriakos E Kypreos
Molecular Genetics, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 280:6276-84. 2005..Substitutions of these residues by alanine provide a recombinant apoE form with improved biological functions... - LCAT can rescue the abnormal phenotype produced by the natural ApoA-I mutations (Leu141Arg)Pisa and (Leu159Arg)FINGeorgios Koukos
Molecular Genetics, Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 46:10713-21. 2007..Both defects can be corrected by treatment with LCAT... - Residues Leu261, Trp264, and Phe265 account for apolipoprotein E-induced dyslipidemia and affect the formation of apolipoprotein E-containing high-density lipoproteinKonstantinos Drosatos
Molecular Genetics, Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 46:9645-53. 2007..Substitution of these residues with Ala improves the apoE functions by preventing hypertriglyceridemia and promoting formation of spherical apoE-containing HDL... - LDL receptor deficiency or apoE mutations prevent remnant clearance and induce hypertriglyceridemia in miceKyriakos E Kypreos
Molecular Genetics, Departments of Medicine and Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA
J Lipid Res 47:521-9. 2006.... - Probing the pathways of chylomicron and HDL metabolism using adenovirus-mediated gene transferVassilis I Zannis
Molecular Genetics, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. vzannis!bu.edu
Curr Opin Lipidol 15:151-66. 2004..Clearance of the lipoprotein remnants and increase in HDL synthesis are obvious targets for therapeutic interventions... - The effects of mutations in helices 4 and 6 of ApoA-I on scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux suggest that formation of a productive complex between reconstituted high density lipoprotein and SR-BI is required for efficienTong Liu
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine and Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 277:21576-84. 2002..Some mutations in apoA-I and/or SR-BI can result in high affinity, but non-productive, binding that does not permit efficient cholesterol efflux... - Molecular mechanisms of type III hyperlipoproteinemia: The contribution of the carboxy-terminal domain of ApoE can account for the dyslipidemia that is associated with the E2/E2 phenotypeKyriakos E Kypreos
Molecular Genetics, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 2394, USA
Biochemistry 42:9841-53. 2003..In contrast, apoE2 exacerbated the hypercholesterolemia and induced hypertriglyceridemia, suggesting that the LDL receptor is the predominant receptor in remnant clearance... - Biophysical properties of apolipoprotein E4 variants: implications in molecular mechanisms of correction of hypertriglyceridemiaIrina N Gorshkova
Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, Massachusetts 02118, USA
Biochemistry 47:12644-54. 2008..The slightly altered structural properties of apoE4-mut2 are associated with slightly reduced binding of this protein to TG-rich lipoprotein particles and milder hypertriglyceridemia as compared with WT apoE4... - Cross-linking and lipid efflux properties of apoA-I mutants suggest direct association between apoA-I helices and ABCA1Angeliki Chroni
Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, 715 Albany Street W509, Boston, Massachusetts 02118, USA
Biochemistry 43:2126-39. 2004..The findings are consistent with a direct association of different combinations of apoA-I helices with a complementary ABCA1 domain. Mutations that alter ABCA1/apoA-I association affect cholesterol efflux and inhibit biogenesis of HDL... - Structure and stability of apolipoprotein a-I in solution and in discoidal high-density lipoprotein probed by double charge ablation and deletion mutationIrina N Gorshkova
Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA
Biochemistry 45:1242-54. 2006..The effects of alterations in the conformation and stability of the apoA-I mutants on in vitro and in vivo functions of apoA-I and lipid homeostasis are discussed... - Generation and characterization of two transgenic mouse lines expressing human ApoE2 in neurons and glial cellsSpiros Georgopoulos
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 41:9293-301. 2002.... - SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol effluxAngeliki Chroni
Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 44:13132-43. 2005..The SR-BI-apoE interactions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-BI and apoE... - A2b adenosine receptor regulates hyperlipidemia and atherosclerosisMilka Koupenova
Department of Medicine, Boston University School of Medicine, 700 Albany St, CVI, W 601, Boston, MA 02118, USA
Circulation 125:354-63. 2012..The cAMP-elevating A(2b) adenosine receptor (A(2b)AR) controls inflammation via its expression in bone marrow cells... - Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiencyAngeliki Chroni
Molecular Genetics, Whitaker Cardiovascular Institute, Department of Medicine, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, Massachusetts 02118, USA
Biochemistry 44:14353-66. 2005..The findings indicate a critical contribution of residue 160 of apoA-I to the in vivo activity of LCAT and the subsequent maturation of HDL and explain the low HDL levels in heterozygous subjects carrying this mutation... - Contribution of the hormone-response elements of the proximal ApoA-I promoter, ApoCIII enhancer, and C/EBP binding site of the proximal ApoA-I promoter to the hepatic and intestinal expression of the ApoA-I and ApoCIII genes in transgenic miceHorng-Yuan Kan
Section of Molecular Genetics, Center for Advanced Biomedical Research, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118-2394, USA
Biochemistry 43:5084-93. 2004..These findings establish the importance of the HREs for the hepatic and intestinal expressions of the apoA-I and apoCIII genes and suggest that C/EBP does not play a central role in the expression of the apoA-I gene... - MicroRNA-370 controls the expression of microRNA-122 and Cpt1alpha and affects lipid metabolismDimitrios Iliopoulos
Department of Biological Chemistry and Molecular Pharmacology, School of Medicine, Harvard University, Boston, MA, USA
J Lipid Res 51:1513-23. 2010.... - Hyperlipidemia in APOE2 transgenic mice is ameliorated by a truncated apoE variant lacking the C-terminal domainGery Gerritsen
Department of Human Genetics, Leiden University Medical Center, The Netherlands
J Lipid Res 44:408-14. 2003..Thus, apoE4-202 is a safe and efficient candidate for future therapeutic applications... - Synergism between nuclear receptors bound to specific hormone response elements of the hepatic control region-1 and the proximal apolipoprotein C-II promoter mediate apolipoprotein C-II gene regulation by bile acids and retinoidsDimitris Kardassis
Department of Basic Sciences, School of Health Sciences, Faculty of Medicine, University of Crete, PO Box 1393, 71500 Heraklion, Greece
Biochem J 372:291-304. 2003.... - Physical and functional interactions between liver X receptor/retinoid X receptor and Sp1 modulate the transcriptional induction of the human ATP binding cassette transporter A1 gene by oxysterols and retinoidsEfstathia Thymiakou
Laboratory of Biochemistry, Department of Basic Sciences, University of Crete Medical School, and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Heraklion, Crete 71110, Greece
Biochemistry 46:11473-83. 2007..Overall, the present study revealed a novel mechanism of regulation of the human ABCA1 transporter which involves synergistic interactions between oxysterol/retinoid-inducible hormone nuclear receptors and the transcription factor Sp1... - Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4Wan Chih Chou
Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Heraklion GR 71110, Greece
Mol Biol Cell 14:1279-94. 2003..Furthermore, the specificity of this interaction for certain target promoters may play an important role in various hepatocyte functions, which are regulated by TGFbeta and the Smads... - Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburideThomas J F Nieland
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
J Lipid Res 45:1256-65. 2004..The reciprocal inhibition of SR-BI and ABCA1 by BLT-4 and glyburide raises the possibility that these proteins may share similar or common steps in their mechanisms of lipid transport... - Inflammatory signaling pathways regulating ApoE gene expression in macrophagesAnca V Gafencu
Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania
J Biol Chem 282:21776-85. 2007.... - ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpressionGery Gerritsen
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
J Lipid Res 46:1466-73. 2005..Thus, Apoc3 deficiency can prevent apoE-induced hyperlipidemia associated with a 10-fold increased hepatic VLDL-TG production rate, most likely by alleviating the apoE-induced inhibition of VLDL-TG hydrolysis... - A dominant negative form of the transcription factor c-Jun affects genes that have opposing effects on lipid homeostasis in miceKonstantinos Drosatos
Department of Basic Sciences, University of Crete Medical School, Heraklion GR 71110, Greece
J Biol Chem 282:19556-64. 2007.... - The carboxy-terminal region of apoA-I is required for the ABCA1-dependent formation of alpha-HDL but not prebeta-HDL particles in vivoAngeliki Chroni
Institute of Biology, National Center for Scientific Research Demokritos, Agia Paraskevi, Athens 15310, Greece
Biochemistry 46:5697-708. 2007.... - Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor kappaB pathwayVarvara Nikolaidou-Neokosmidou
Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, Heraklion 71003, Crete, Greece
Biochem J 398:439-50. 2006.... - Identification of the molecular target of small molecule inhibitors of HDL receptor SR-BI activityThomas J F Nieland
Department of Biology, Massachusetts Institute of Technology, Room 68 483, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Biochemistry 47:460-72. 2008..Consequently, BLTs may help determine the therapeutic potential of SR-BI-targeted pharmaceutical drugs... - Biophysical analysis of progressive C-terminal truncations of human apolipoprotein E4: insights into secondary structure and unfolding propertiesAngeliki Chroni
Institute of Biology, National Centre for Scientific Research Demokritos, Aghia Paraskevi, Athens 15310, Greece
Biochemistry 47:9071-80. 2008.... - Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitroRoshni R Singaraja
Center for Molecular Medicine and Therapeutics, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia, Canada
Circ Res 99:389-97. 2006....
Research Grants
- Functions of apoE in cholesterol and triglyceride homeostasisVassilis I Zannis; Fiscal Year: 2010..Gene transfer in single or double knockout mice for apoA-l, apoE, SR-BI and biochemical analyses will be employed in these studies. ..
- APOLIPOPROTEIN VARIATION AND HUMAN DISEASEVassilis Zannis; Fiscal Year: 2003..Thus the information obtained from this project may provide rational approaches towards correcting low plasma HDL levels and reducing hypertriglyceridemia in humans. ..
- ANALYSIS OF HUMAN APOLIPOPROTEIN A-IVassilis Zannis; Fiscal Year: 2002..Understanding the biological functions of apoA-I and HDL which are relevant to the development of CAD may lead to new pharmacological approaches to prevent and/or treat these conditions. ..
- ApoE in Cholesterol and Triglyceride HomeostasisVassilis Zannis; Fiscal Year: 2004..We expect that apoE forms that can clear cholesterol and triglycerides and protect from atherosclerosis may provide new therapeutic tools in the near future for the correction of remnant removal disorders. ..
- Molecular and Funcitonal Analysis of Human A-IVassilis I Zannis; Fiscal Year: 2010..This information is important in the design of new pharmaceuticals to increase HDL levels while preserving the atheroprotective functions of HDL and thus decrease the risk for cardiovascular disease. ..
- Functions of apoE in cholesterol and triglyceride homeostasisVassilis Zannis; Fiscal Year: 2007..Gene transfer in single or double knockout mice for apoA-l, apoE, SR-BI and biochemical analyses will be employed in these studies. ..
- Molecular and Functional Analysis of Human ApoA-1Vassilis Zannis; Fiscal Year: 2006..Understanding the molecular structure and the various biological functions of apoA-I may lead to new pharmacological approaches to prevent and/or treat these conditions. ..
- APOLIPOPROTEIN VARIATION AND HUMAN DISEASEVassilis Zannis; Fiscal Year: 1999..Thus the information obtained from this project may provide rational approaches towards correcting low plasma HDL levels and hypertriglyceridemia. ..
- APOLIPOPROTEIN VARIATION AND HUMAN DISEASEVassilis Zannis; Fiscal Year: 1993..The information which will emerge may then provide rational means of controlling plasma lipoprotein levels in ways that are protective against atherosclerosis...
- APOPROTEIN VARIATION AND HUMAN DISEASEVassilis Zannis; Fiscal Year: 1990..The proposed research will enhance our knowledge of new molecular aspects of lipoprotein metabolism which may be relevant to human diseases and will contribute towards better diagnoses and treatment of these conditions...