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Prenatal stress enhances severity of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring via inflammatory pathways

Published online by Cambridge University Press:  01 November 2012

H. Ho ,
S. Lhotak ,
M. E. Solano ,
K. Karimi ,
M. K. Pincus ,
R. C. Austin  and
P. Arck
H. Ho
Affiliation:
Department of Medicine, Brain-Body-Institute, McMaster University, Hamilton, Ontario, Canada
S. Lhotak
Affiliation:
Department of Medicine, Division of Nephrology, St. Joseph's Healthcare Hamilton, McMaster University, Ontario, Canada
M. E. Solano
Affiliation:
Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Fetomaternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
K. Karimi
Affiliation:
Department of Medicine, Brain-Body-Institute, McMaster University, Hamilton, Ontario, Canada
M. K. Pincus
Affiliation:
Department of Pediatrics, Division of Pneumology and Immunology, Charité University Medical Center, Berlin, Germany
R. C. Austin
Affiliation:
Department of Medicine, Division of Nephrology, St. Joseph's Healthcare Hamilton, McMaster University, Ontario, Canada
P. Arck*
Affiliation:
Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Fetomaternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
*
*Address for correspondence: Dr P. Arck, MD, Labor fuer Experimentelle Feto-Maternale Medizin, Klinik für Geburtshilfe und Praenatalmedizin, Martinistr, 52, 20246 Hamburg, Germany. Email p.arck@uke.de
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Abstract

Atherosclerosis is the underlying cause of cardiovascular disease and stroke. Endothelial cell dysfunctions are early events in atherosclerosis, resulting in the recruitment of circulating monocytes. The immune system can elicit an inflammatory response toward the atherosclerotic lesion, thereby accelerating lesion growth. Risk factors for atherosclerosis include hypertension, smoking, stress perception or low birth weight. As prenatal stress challenge decreases the birth weight and affects the offspring's postnatal immune response, we aimed to investigate whether prenatal stress contributes to the development of atherosclerosis in mice. Syngenic pregnant apolipoprotein E-deficient (apoE−/−) dams were exposed to sound stress on gestation days 12.5 and 14.5. The presence and size of atherosclerotic plaques in the offspring at the age of 15 weeks was evaluated by histomorphology, accompanied by flow cytometric analysis of the frequency and phenotype of monocytes/macrophages and regulatory T (Treg) cells in the blood. Further, cytokine secretion of peripheral blood lymphocytes was analyzed. In response to prenatal stress challenge, an increased frequency of large atherosclerotic plaques was detectable in apoE−/− offspring, which was particularly profound in females. Prenatal stress also resulted in alterations of the offspring's immune response, such as a decreased frequency of Treg cells in blood, alterations of macrophage populations in blood and an increased secretion of inflammatory cytokines. We provide novel evidence that prenatally stressed adult offspring show an increased severity of atherosclerosis. As Treg cells are key players in dampening inflammation, the observed increase in atherosclerosis may be due to the lack of Treg cell frequency. Future interdisciplinary research is urgently required to understand the developmental origin of prenatal stress-induced atherosclerosis. The availability of our model may facilitate and foster such research endeavors.

Keywords

apoE−/−atherosclerosisinflammationplaquesprenatal stress
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 1 , February 2013 , pp. 90 - 97
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

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