Substitution of the carboxyl-terminal domain of apo AI with apo AII sequences restores the potential of HDL to reduce the progression of atherosclerosis in apo E knockout mice

The Journal of Clinical Investigation
P HolvoetD Collen

Abstract

HDL metabolism and atherosclerosis were studied in apo E knockout (KO) mice overexpressing human apo AI, a des- (190-243)-apo AI carboxyl-terminal deletion mutant of human apo AI or an apo AI-(1-189)-apo AII-(12-77) chimera in which the carboxyl-terminal domain of apo AI was substituted with the pair of helices of apo AII. HDL cholesterol levels ranked: apo AI/apo E KO approximately apo AI-(1-189)-apo AII- (12-77)/apo E KO > > des-(190-243)-apo AI/apo E KO > apo E KO mice. Progression of atherosclerosis ranked: apo E KO > des-(190-243)-apo AI/apo E KO > > apo AI-(1-189)- apo AII-(12-77)/apo E KO approximately apo AI/apo E KO mice. Whereas the total capacity to induce cholesterol efflux from lipid-loaded THP-1 macrophages was higher for HDL of mice overexpressing human apo AI or the apo AI/apo AII chimera, the fractional cholesterol efflux rate, expressed in percent cholesterol efflux/microg apolipoprotein/h, for HDL of these mice was similar to that for HDL of mice overexpressing the deletion mutant and for HDL of apo E KO mice. This study demonstrates that the tertiary structure of apo AI, e.g., the number and organization of its helices, and not its amino sequence is essential for protection against atherosclerosis because it...Continue Reading

References

Nov 9, 1989·The New England Journal of Medicine·D J Gordon, B M Rifkind
Feb 1, 1987·Infusionstherapie Und Klinische Ernährung·G KleinbergerK Lenz
Mar 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·G Assmann, H B Brewer
Jan 1, 1982·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·E J SchaeferH B Brewer
Aug 1, 1980·International Journal of Cancer. Journal International Du Cancer·S TsuchiyaK Tada
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·A S PlumpJ L Breslow
Aug 1, 1994·The Journal of Clinical Investigation·C PásztyE M Rubin
Jan 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·Y NakashimaR Ross
Jan 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·R L ReddickN Maeda
Mar 15, 1996·The Journal of Biological Chemistry·E L GongE M Rubin

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Citations

Oct 8, 1999·Clinica Chimica Acta; International Journal of Clinical Chemistry·J DavignonL Bernier
Jul 17, 1999·Atherosclerosis·O Stein, Y Stein
Apr 29, 2000·Current Opinion in Lipidology·A D Kalopissis, J Chambaz
Jul 15, 2009·Biochimica Et Biophysica Acta·Jinko SawashitaKeiichi Higuchi
Apr 5, 2012·The Journal of Pharmacy and Pharmacology·Tomoyuki YasudaTatsuro Ishida
Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G TheilmeierP Holvoet
Oct 20, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A Mertens, P Holvoet

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