Document Detail

Maternal hypercholesterolemia enhances atherogenesis in normocholesterolemic rabbits, which is inhibited by antioxidant or lipid-lowering intervention during pregnancy: an experimental model of atherogenic mechanisms in human fetuses.
MedLine Citation:
PMID:  11073892     Owner:  NLM     Status:  MEDLINE    
Maternal hypercholesterolemia during pregnancy is associated with a marked increase in aortic fatty streak formation in human fetuses and faster progression of atherosclerosis during normocholesterolemic childhood. However, the mechanisms responsible are unknown, and the contribution of genetic differences is difficult to assess in humans. The goal of this study was to determine whether maternal hypercholesterolemia per se may cause enhanced fatty streak formation in offspring and whether interventions during pregnancy can reduce it. During pregnancy, 1 group of New Zealand White rabbits was fed control chow and 8 groups were fed hypercholesterolemic diets Chol 1 (yielding plasma cholesterol of 153 mg/dL) or Chol 2 (yielding 359 mg/dL) without or with cholestyramine, vitamin E, or both. Offspring (n=15 to 25 per group) were killed at birth. Maternal hypercholesterolemia enhanced mean lesion size in the aorta of their offspring at birth from 44+/-18x10(3) micrometer(2) per section in controls to 85+/-26x10(3) in Chol 1 and 156+/-49x10(3) in Chol 2 groups (P<0.0001 for both). Cholestyramine or vitamin E treatment of mothers significantly reduced atherosclerosis at birth by up to 39% compared with controls on the same diet. Oxidized fatty acids and malondialdehyde in aortic atherosclerotic lesions and plasma were similarly affected by diets and treatment as atherosclerosis. Our results establish the causal role of hypercholesterolemia and peroxidation in fetal atherogenesis and demonstrate that both lipid-lowering and antioxidant interventions during pregnancy can reduce it. If it can be established that interventions in mothers also affect progression of lesions after birth, this may indicate a novel approach for the prevention of atherosclerosis.
C Napoli; J L Witztum; F Calara; F de Nigris; W Palinski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  87     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-17     Completed Date:  2000-11-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  946-52     Citation Subset:  IM    
Department of Medicine, University of California San Diego, La Jolla, California, USA.
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MeSH Terms
Antioxidants / administration & dosage
Aorta / drug effects,  pathology
Arteriosclerosis / blood,  congenital*,  pathology,  prevention & control*
Cholesterol / blood
Cholesterol, Dietary / pharmacology
Cholestyramine Resin / administration & dosage*
Diet, Atherogenic
Fatty Acids / metabolism
Fetus / drug effects,  metabolism,  pathology
Hypercholesterolemia / blood,  drug therapy*
Lipid Peroxidation / drug effects
Pregnancy Complications / blood,  drug therapy*
Prenatal Exposure Delayed Effects*
Remission Induction
Triglycerides / blood
Vitamin E / administration & dosage*
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Cholesterol, Dietary; 0/Fatty Acids; 0/Triglycerides; 11041-12-6/Cholestyramine Resin; 1406-18-4/Vitamin E; 57-88-5/Cholesterol

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