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Probucol impairs cardiac function in apo E‐KO mice
Author(s) -
Moghadasian Mohammed H,
Othman Rgia,
Jassal Davinder,
Fang Tielan,
Zhao Zhaohui,
Kroeker Amy,
Riediger Natalie,
Xu Zuyuan,
Walker Kristy,
Le Khoung,
Azordegan Nazila
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1116.7
Subject(s) - probucol , medicine , endocrinology , ejection fraction , cardiac function curve , cholesterol , apolipoprotein b , chemistry , antioxidant , heart failure , biochemistry
Background: Despite beneficial cholesterol‐lowering and antioxidant properties of probucol, it paradoxically increases coronary atherogenesis in apo E‐KO mice. The aim of this study was to investigate the effects of probucol on cardiac function in apo E‐KO mice. Materials and Methods: Male apo E‐KO and C57BL/6 mice were fed an atherogenic diet with (treated, n=8) or without (control, n=8) 1% probucol for 16 weeks. Plasma cholesterol levels were measured. Murine echocardiography was performed serially at 6 week intervals. Results: Probucol treatment resulted in significant reductions in plasma cholesterol levels in both apo E‐KO (−30%, p<0.05) and C57BL/6 mice (−90%, p<0.01). Apo E‐KO mice treated with probucol showed early regional LV systolic dysfunction as early as 6 weeks with further decrease over time [endocardial velocity −40%; strain −40%, ejection fraction −10% (p<0.01)], with no impact on mortality. Such effects of probucol were not observed in C57BL/6 mice. Conclusions: Probucol impairs cardiac function in apo E‐KO mice. This may be related to previously observed coronary atherogenesis due to probucol in this animal model. Supported in part by URGP, HSF and NSERC.