on June 3, 2004
Published online before print June 3, 2004, doi: 10.1161/01.ATV.0000134297.61979.3c
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Submitted on January 15, 2004
Accepted on May 20, 2004
Subphysiologic Apolipoprotein E (ApoE) Plasma Levels Inhibit Neointimal Formation After Arterial Injury in ApoE-Deficient Mice
Hilke Wientgen ;
From the Departments of Medicine (E.A.F.)/Division of Endocrinology (H.W.), and Biomathematics/Biostatistics (L.R.), and Pathology (J.T.F.), and the Zena and Michael A. Wiener Cardiovascular Institute (S.O., J.T.F., E.A.F.), Mount Sinai School of Medicine, New York, NY; the Department of Pharmacological Sciences (F.E.T., D.L.W.), State University of New York at Stony Brook, Stony Brook, NY; and the Department of Medicine, Division of Cardiology (E.A.F.), New York University School of Medicine, New York, NY.
* To whom correspondence should be addressed. E-mail: edward.fisher{at}med.nyu.edu.
Objective--Apolipoprotein E (apoE) reduces mouse atherosclerosis progression independent of plasma cholesterol level effects. A mouse artery injury model was used to examine whether apoE exhibits beneficial lipid-independent effects on neointimal formation.
Methods and Results--ApoE-deficient (apoE-/-), wild-type (WT), and transgenic apoE-/- mice (secreting apoE at different levels from adrenal glands) underwent femoral artery injury. Mice with low expression of plasma apoE (0.1% of WT) had cholesterol levels approximately half those of apoE-/- littermates (but still 
6x >WT). Mice with a high expression (HE; 2% to 3% of WT) of plasma apoE had cholesterol levels approximately twice those of WT. Injured WT mouse (versus apoE-/-) arteries had a smaller mean intima-to-media (I/M) ratio (0.88 versus 1.96; P<0.05). HE mice tended to have lower mean I/M ratios (1.3; P>0.05 versus apoE-/- mice). Multiple regression analysis indicated that apoE levels were significantly associated with reduced I/M ratios, but plasma cholesterol levels were not, before or after adjusting for apoE. In addition, foam cell content of the neointima and media of injured arteries, a negative prognostic indicator in postangioplasty human lesions, was inversely related to plasma apoE levels.
Conclusions--Similar to its effects on atherosclerosis progression, in a mouse model of restenosis, a subphysiological level of apoE was associated with beneficial effects on lesion size/composition.
Key words: apolipoprotein E • arterial injury • neointimal formation • restenosis • mouse
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