Poor maternal nutrition programmes a pro-atherosclerotic phenotype in ApoE−/−mice

Blackmore, H.L., Piekarz, A.V., Fernandez‑Twinn, D.S., Mercer, J.R. , Figg, N., Bennett, M. and Ozanne, S.E. (2012) Poor maternal nutrition programmes a pro-atherosclerotic phenotype in ApoE−/−mice. Clinical Science, 123(4), pp. 251-257. (doi: 10.1042/CS20110487)

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Abstract

Numerous animal studies have consistently shown that early life exposure to LP (low-protein) diet programmes risk factors for CVD (cardiovascular disease) such as dyslipidaemia, high BP (blood pressure) and cardiac dysfunction in the offspring. However, studies on the effect of maternal under-nutrition on offspring development of atherosclerosis are scarce. Applying our LP model to the ApoE−/− atherosclerosis-prone mouse model, we investigated the development of atherosclerotic lesions in the aortic root of 6-month-old offspring. In addition, markers of plaque progression including SMA (smooth muscle actin) and Mac3 (macrophage marker 3) were studied. Pregnant dams were fed on a control (20% protein) or on an isocaloric LP diet (8% protein) throughout pregnancy and lactation. After weaning, male offspring were maintained on 20% normal laboratory chow. At 6 months of age, LP offspring showed a significantly greater plaque area (P<0.05) with increased cholesterol clefts and significantly higher indices of DNA damage compared with controls (P<0.05). The expression of HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) (P<0.05) and LDL (low-density lipoprotein) receptor in the liver of LP offspring were increased. Furthermore, LP offspring had higher LDL-cholesterol levels (P<0.05) and a trend towards elevated insulin. There were no differences in other lipid measurements and fasting glucose between groups. These observations suggest that early exposure to an LP diet accelerates the development and increases the progression of atherosclerotic lesions in young adult offspring. Future studies are needed to elucidate the specific mechanisms linking in utero exposure to a diet low in protein to the development of atherosclerosis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mercer, Dr John
Authors: Blackmore, H.L., Piekarz, A.V., Fernandez‑Twinn, D.S., Mercer, J.R., Figg, N., Bennett, M., and Ozanne, S.E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press Ltd.
ISSN:0143-5221
ISSN (Online):1470-8736
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in Clinical Science 123(4):251-257
Publisher Policy:Reproduced under a Creative Commons License

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