Dr. Zannis is Emeritus Professor of Cardiovascular Medicine at Boston University School of Medicine. The major focus of his research is on the structure and functions of apoA-I and apoE in relation to the biogenesis of HDL, atherosclerosis and Alzheimer's disease. Using adenovirus-mediated gene transfer in apoA-I-deficient mice, we have established that apoA-I mutations inhibit discrete steps in a pathway that leads to the biogenesis and remodeling of HDL. To this point, five discrete categories of apoA-I mutants have been characterized that may affect the interactions of apoA-I with ABCA1 or LCAT or may influence the plasma PLTP activity or may cause various forms of dyslipidemia. Biogenesis of HDL is not a unique property of apoA-I. Using adenovirus-mediated gene transfer of apoE in apoA-I- or ABCA1-deficient mice, we have established that apoE also participates in a novel pathway of biogenesis of apoE-containing HDL particles. This process requires the functions of the ABCA1 lipid transporter and LCAT and it is promoted by substitution of hydrophobic residues in the 261 to 269 region of apoE by Ala. 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.
Boston University School of Medicine
Evans Center for Interdisciplinary Biomedical Research
Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences
Apolipoprotein Variation and Human Disease
05/01/2000 - 04/30/2005 (PI)
NIH/National Heart, Lung, and Blood Institute
5 R01 HL33952 19
Role of ApoE in Cholesterol and Triglyceride Homeostasis
11/01/2001 - 06/30/2004 (PI)
ApoE Functions Relevant to AD and Gene Transfer to the Brain Using Recombinant Viral Vectors
09/01/2000 - 08/31/2003 (PI)
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Theofilatos D, Fotakis P, Valanti E, Sanoudou D, Zannis V, Kardassis D. HDL-apoA-I induces the expression of angiopoietin like 4 (ANGPTL4) in endothelial cells via a PI3K/AKT/FOXO1 signaling pathway. Metabolism. 2018 10; 87:36-47. PMID: 29928895
Dafnis I, Raftopoulou C, Mountaki C, Megalou E, Zannis VI, Chroni A. ApoE isoforms and carboxyl-terminal-truncated apoE4 forms affect neuronal BACE1 levels and Aß production independently of their cholesterol efflux capacity. Biochem J. 2018 05 31; 475(10):1839-1859. PMID: 29743204
Kelley M, Zannis VI, Hussain MM. Synthesis of HDL apolipoproteins by rat hepatocytes. 2018.
Zannis VI, Su S, Fotakis P. Role of apolipoproteins, ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins. J Biomed Res. 2017 Nov 04. PMID: 29109329
Daminelli EN, Fotakis P, Mesquita CH, Maranhão RC, Zannis VI. Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice. Lipids. 2017 Dec; 52(12):991-998. PMID: 29094255
Jauhiainen M, Dafnis I, Metso J, Zannis VI, Chroni A. Effects of apoE variants on PLTP interaction and activation of low and high activity forms of PLTP. Atherosclerosis. 2016; 252:e118. View Publication
Tamehiro N, Park MH, Hawxhurst V, Nagpal K, Adams ME, Zannis VI, Golenbock DT, Fitzgerald ML. LXR Agonism Upregulates the Macrophage ABCA1/Syntrophin Protein Complex That Can Bind ApoA-I and Stabilized ABCA1 Protein, but Complex Loss Does Not Inhibit Lipid Efflux. Biochemistry. 2015 Nov 24; 54(46):6931-41. PMID: 26506427; PMCID: PMC4874254; DOI: 10.1021/acs.biochem.5b00894;
Dafnis I, Metso J, Zannis VI, Jauhiainen M, Chroni A. Influence of Isoforms and Carboxyl-Terminal Truncations on the Capacity of Apolipoprotein E To Associate with and Activate Phospholipid Transfer Protein. Biochemistry. 2015 Sep 29; 54(38):5856-66. PMID: 26337529; DOI: 10.1021/acs.biochem.5b00681;
Tiniakou I, Kanaki Z, Georgopoulos S, Chroni A, Van Eck M, Fotakis P, Zannis VI, Kardassis D. Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice. Atherosclerosis. 2015 Nov; 243(1):77-85. PMID: 26363436; DOI: 10.1016/j.atherosclerosis.2015.08.028;
Fotakis P, Kuivenhoven JA, Dafnis E, Kardassis D, Zannis VI. The Effect of Natural LCAT Mutations on the Biogenesis of HDL. Biochemistry. 2015 Jun 2; 54(21):3348-59. PMID: 25948084; DOI: 10.1021/acs.biochem.5b00180;
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