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The peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ciprofibrate inhibits apolipoprotein B mRNA editing in low density lipoprotein receptor-deficient mice: effects on plasma lipoproteins and the development of atherosclerotic lesions.
J Biol Chem. 2004 Jul 02; 279(27):28662-9.JB

Abstract

Low density lipoprotein receptor (LDLR)-deficient mice fed a chow diet have a mild hypercholesterolemia caused by the abnormal accumulation in the plasma of apolipoprotein B (apoB)-100- and apoB-48-carrying intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). Treatment of LDLR-deficient mice with ciprofibrate caused a marked decrease in plasma apoB-48-carrying IDL and LDL but at the same time caused a large accumulation of triglyceride-depleted apoB-100-carrying IDL and LDL, resulting in a significant increase in plasma cholesterol levels. These plasma lipoprotein changes were associated with an increase in the hepatic secretion of apoB-100-carrying very low density lipoproteins (VLDL) and a decrease in the secretion of apoB-48-carrying VLDL, accompanied by a significant decrease in hepatic apoB mRNA editing. Hepatic apobec-1 complementation factor mRNA and protein abundance were significantly decreased, whereas apobec-1 mRNA and protein abundance remained unchanged. No changes in apoB mRNA editing occurred in the intestine of the treated animals. After 150 days of treatment with ciprofibrate, consistent with the increased plasma accumulation of apoB-100-carrying IDL and LDL, the LDLR-deficient mice displayed severe atherosclerotic lesions in the aorta. These findings demonstrate that ciprofibrate treatment decreases hepatic apoB mRNA editing and alters the pattern of hepatic lipoprotein secretion toward apoB-100-associated VLDL, changes that in turn lead to increased atherosclerosis.

Authors+Show Affiliations

Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15123680

Citation

Fu, Tao, et al. "The Peroxisome Proliferator-activated Receptor Alpha (PPARalpha) Agonist Ciprofibrate Inhibits Apolipoprotein B mRNA Editing in Low Density Lipoprotein Receptor-deficient Mice: Effects On Plasma Lipoproteins and the Development of Atherosclerotic Lesions." The Journal of Biological Chemistry, vol. 279, no. 27, 2004, pp. 28662-9.
Fu T, Mukhopadhyay D, Davidson NO, et al. The peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ciprofibrate inhibits apolipoprotein B mRNA editing in low density lipoprotein receptor-deficient mice: effects on plasma lipoproteins and the development of atherosclerotic lesions. J Biol Chem. 2004;279(27):28662-9.
Fu, T., Mukhopadhyay, D., Davidson, N. O., & Borensztajn, J. (2004). The peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ciprofibrate inhibits apolipoprotein B mRNA editing in low density lipoprotein receptor-deficient mice: effects on plasma lipoproteins and the development of atherosclerotic lesions. The Journal of Biological Chemistry, 279(27), 28662-9.
Fu T, et al. The Peroxisome Proliferator-activated Receptor Alpha (PPARalpha) Agonist Ciprofibrate Inhibits Apolipoprotein B mRNA Editing in Low Density Lipoprotein Receptor-deficient Mice: Effects On Plasma Lipoproteins and the Development of Atherosclerotic Lesions. J Biol Chem. 2004 Jul 2;279(27):28662-9. PubMed PMID: 15123680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ciprofibrate inhibits apolipoprotein B mRNA editing in low density lipoprotein receptor-deficient mice: effects on plasma lipoproteins and the development of atherosclerotic lesions. AU - Fu,Tao, AU - Mukhopadhyay,Debnath, AU - Davidson,Nicholas O, AU - Borensztajn,Jayme, Y1 - 2004/04/27/ PY - 2004/5/5/pubmed PY - 2004/8/12/medline PY - 2004/5/5/entrez SP - 28662 EP - 9 JF - The Journal of biological chemistry JO - J Biol Chem VL - 279 IS - 27 N2 - Low density lipoprotein receptor (LDLR)-deficient mice fed a chow diet have a mild hypercholesterolemia caused by the abnormal accumulation in the plasma of apolipoprotein B (apoB)-100- and apoB-48-carrying intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). Treatment of LDLR-deficient mice with ciprofibrate caused a marked decrease in plasma apoB-48-carrying IDL and LDL but at the same time caused a large accumulation of triglyceride-depleted apoB-100-carrying IDL and LDL, resulting in a significant increase in plasma cholesterol levels. These plasma lipoprotein changes were associated with an increase in the hepatic secretion of apoB-100-carrying very low density lipoproteins (VLDL) and a decrease in the secretion of apoB-48-carrying VLDL, accompanied by a significant decrease in hepatic apoB mRNA editing. Hepatic apobec-1 complementation factor mRNA and protein abundance were significantly decreased, whereas apobec-1 mRNA and protein abundance remained unchanged. No changes in apoB mRNA editing occurred in the intestine of the treated animals. After 150 days of treatment with ciprofibrate, consistent with the increased plasma accumulation of apoB-100-carrying IDL and LDL, the LDLR-deficient mice displayed severe atherosclerotic lesions in the aorta. These findings demonstrate that ciprofibrate treatment decreases hepatic apoB mRNA editing and alters the pattern of hepatic lipoprotein secretion toward apoB-100-associated VLDL, changes that in turn lead to increased atherosclerosis. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15123680/The_peroxisome_proliferator_activated_receptor_alpha__PPARalpha__agonist_ciprofibrate_inhibits_apolipoprotein_B_mRNA_editing_in_low_density_lipoprotein_receptor_deficient_mice:_effects_on_plasma_lipoproteins_and_the_development_of_atherosclerotic_lesions_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15123680 DB - PRIME DP - Unbound Medicine ER -