Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice

The Journal of Clinical Investigation
S H ZhangN Maeda

Abstract

Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%, respectively. Paradoxically, however, aortic atherosclerotic plaques in the probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/- mice, and the lesions were two to four times larger and more mature regardless of sex, age, and genetic background (P < 10(-)6). Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation. Probucol treatment also accelerated lesion development in apoE+/- mice fed an atherogenic diet, indicating that the adverse effect is not dependent on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice, but do not have accelerated plaque development. Thus, the enhanced atherosclerosis in the probucol-treated animals is unlikely to be caused by the reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma c...Continue Reading

References

Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R WilliamsonN Maeda
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J A PiedrahitaN Maeda
Jan 1, 1991·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·I BjörkhemP Henriksson
Feb 1, 1991·Clinical Cardiology·C J SchwartzR M Nerem
Nov 9, 1989·The New England Journal of Medicine·D J Gordon, B M Rifkind
Dec 1, 1987·Atherosclerosis·B PaigenR A Williams
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·T KitaC Kawai
Jun 27, 1986·The American Journal of Cardiology·D Steinberg
Jun 27, 1986·The American Journal of Cardiology·A YamamotoB Kishino
Feb 1, 1986·The Journal of Clinical Investigation·S ParthasarathyD Steinberg
Jan 1, 1986·Japanese Journal of Pharmacology·K TawaraY Abiko
Oct 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·R K TangiralaW Palinski
Aug 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·L S ElinderG Walldius
Sep 1, 1995·The Journal of Clinical Investigation·M J CallowE M Rubin
Sep 1, 1994·The Journal of Clinical Investigation·S H ZhangN Maeda
May 1, 1994·The Journal of Clinical Investigation·S IshibashiD K Burns
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

❮ Previous
Next ❯

Citations

Jul 23, 1999·BioFactors·S R ThomasR Stocker
Aug 7, 2001·Current Atherosclerosis Reports·S ParthasarathyN Santanam
May 17, 2005·Methods : a Companion to Methods in Enzymology·Alan Daugherty, Debra L Rateri
Jan 30, 2002·Clinica Chimica Acta; International Journal of Clinical Chemistry·Seon Min JeonMyung Sook Choi
Oct 8, 1999·Clinica Chimica Acta; International Journal of Clinical Chemistry·J DavignonL Bernier
Jul 17, 1999·Atherosclerosis·O Stein, Y Stein
Oct 18, 2000·Free Radical Biology & Medicine·P K WittingR Stocker
Aug 18, 2000·Free Radical Biology & Medicine·G M Chisolm, D Steinberg
Nov 1, 2001·Trends in Cardiovascular Medicine·D Praticò
Nov 1, 2001·Trends in Cardiovascular Medicine·E Meagher, D J Rader
Nov 1, 2001·Trends in Cardiovascular Medicine·J L Witztum, D Steinberg
Sep 13, 2001·Clinical and Experimental Pharmacology & Physiology·Y KondoS Murakami
May 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Anne BraunMonty Krieger
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Q XiaoJ L Degen
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·O CynshiT Kodama
Aug 23, 2006·The British Journal of Nutrition·Thierry SoulatLudovic Drouet
Aug 25, 2009·Human Reproduction Update·Victor Y FujimotoRichard W Browne
Apr 29, 1998·Current Opinion in Lipidology·M Fisher, P H Groves
Nov 13, 1998·Current Opinion in Lipidology·K J Williams, I Tabas
Feb 19, 2000·Current Opinion in Lipidology·R Stocker
Jul 6, 2000·Current Opinion in Lipidology·M J Thomas
Aug 17, 2001·Current Opinion in Lipidology·R MashimaR Stocker
Aug 17, 1999·Annual Review of Nutrition·I Tabas
Jun 8, 1999·The Journal of Clinical Investigation·D Steinberg
Jul 20, 1999·The Journal of Clinical Investigation·J W Heinecke
Mar 15, 2008·Redox Report : Communications in Free Radical Research·David TanousRoland Stocker
Jun 15, 2011·Bioscience, Biotechnology, and Biochemistry·Katsumi Imaizumi
Sep 15, 1998·Free Radical Research·N Noguchi, E Niki
Jan 1, 2016·Biochimie·R SalvayreC Camaré
Sep 20, 2008·Free Radical Biology & Medicine·Sylvain GalvaniAnne Nègre-Salvayre

❮ Previous
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