https://scholars.lib.ntu.edu.tw/handle/123456789/454609
Title: | A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit | Authors: | Liaw Y.-W. Lin C.-Y. Lai Y.-S. Yang T.-C. Wang C.-J. Whang-Peng J. Liu L.F. Lin C.-P. Nieh S. SHAO-CHUN LU Hwang J. |
Issue Date: | 2014 | Publisher: | Public Library of Science | Journal Volume: | 9 | Journal Issue: | 12 | Source: | PLoS ONE | Abstract: | Low HDL-C levels are associated with atherosclerosis and non-alcoholic steatohepatitis, and increased levels may reduce the risk of these diseases. Inhibition of cholesteryl ester transfer protein (CETP) activity is considered a promising strategy for increasing HDL-C levels. Since CETP is a self-antigen with low immunogenicity, we developed a novel CETP vaccine (Fc-CETP6) to overcome the low immunogenicity of CETP and for long-term inhibition of CETP activity. The vaccine consists of a rabbit IgG Fc domain for antigen delivery to antigen-presenting cells fused to a linear array of 6 repeats of a CETP epitope to efficiently activate B cells. Rabbits were fed a high fat/cholesterol (HFC) diet to induce atherosclerosis and NASH, and immunized with Fc-CETP6 vaccine. The Fc-CETP6 vaccine successfully elicited anti-CETP antibodies and lowered plasma CETP activity. The levels of plasma HDL-C and ApoA-I were higher, and plasma ox-LDL lower, in the Fc-CETP6-immunized rabbits as compared to the unimmunized HFC diet-fed rabbits. Pathological analyses revealed less lipid accumulation and inflammation in the aorta and liver of the Fc-CETP6-immunized rabbits. These results show that the Fc-CETP6 vaccine efficiently elicited antibodies against CETP and reduced susceptibility to both atherosclerosis and steatohepatitis induced by the HFC diet. Our findings suggest that the Fc-CETP6 vaccine may improve atherosclerosis and NASH and has high potential for clinical use. ? 2014 Liaw et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84915747326&doi=10.1371%2fjournal.pone.0111529&partnerID=40&md5=28a58fc218607128d17baae1faacab6b https://scholars.lib.ntu.edu.tw/handle/123456789/454609 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0111529 | SDG/Keyword: | apolipoprotein A1; cholesterol; cholesterol ester transfer protein; cholesterol ester transfer protein antibody; fc cholesterol ester transfer protein 6 vaccine; high density lipoprotein cholesterol; oxidized low density lipoprotein; protein antibody; unclassified drug; vaccine; antibody; apolipoprotein A1; cholesterol; cholesterol ester transfer protein; hybrid protein; immunoglobulin Fc fragment; low density lipoprotein; oxidized low density lipoprotein; vaccine; animal cell; animal experiment; animal model; animal tissue; antibody production; aortic inflammation; Article; atherosclerosis; cholesterol blood level; cholesterol diet; controlled study; drug efficacy; enzyme activity; female; hepatitis; immunization; immunogenicity; inflammation; lipid diet; lipid storage; lipoprotein blood level; liver fibrosis; macrophage migration; nonalcoholic fatty liver; nonhuman; protein blood level; adverse effects; animal; atherosclerosis; blood; disease model; fibrosis; gene expression; genetics; human; immunology; lipid diet; metabolism; Non-alcoholic Fatty Liver Disease; pathology; rabbit; Oryctolagus cuniculus; Animals; Antibodies; Apolipoprotein A-I; Atherosclerosis; Cholesterol; Cholesterol Ester Transfer Proteins; Diet, High-Fat; Disease Models, Animal; Female; Fibrosis; Gene Expression; Humans; Immunoglobulin Fc Fragments; Lipoproteins, LDL; Non-alcoholic Fatty Liver Disease; Rabbits; Recombinant Fusion Proteins; Vaccines |
Appears in Collections: | 生物化學暨分子生物學科研究所 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.