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Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring

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Abstract

The maternal system is challenged with many physiological changes throughout pregnancy to prepare the body to meet the metabolic needs of the fetus and for delivery. Many pregnancies, however, are faced with pathological stressors or complications that significantly impact maternal health. A shift in this paradigm is now beginning to investigate the implication of pregnancy complications on the fetus and their continued influence on offspring disease risk into adulthood. In this investigation, we sought to determine whether maternal hypertension during pregnancy alters the cerebral response of adult offspring to acute ischemic stroke. Atrial natriuretic peptide gene-disrupted (ANP−/−) mothers exhibit chronic hypertension that escalates during pregnancy. Through comparison of heterozygote offspring born from either normotensive (ANP+/−WT) or hypertensive (ANP+/−KO) mothers, we have demonstrated that offspring exposed to maternal hypertension exhibit larger cerebral infarct volumes following middle cerebral artery occlusion. Observation of equal baseline cardiovascular measures, cerebrovascular structure, and cerebral blood volumes between heterozygote offspring suggests no added influences on offspring that would contribute to adverse cerebral response post-stroke. Cerebral mRNA expression of endothelin and nitric oxide synthase vasoactive systems demonstrated up-regulation of Et-1 and Nos3 in ANP+/−KO mice and thus an enhanced acute vascular response compared to ANP+/−WT counterparts. Gene expression of Na+/K+ ATPase channel isoforms, Atp1a1, Atp1a3, and Atp1b1, displayed no significant differences. These investigations are the first to demonstrate a fetal programming effect between maternal hypertension and adult offspring stroke outcome. Further mechanistic studies are required to complement epidemiological evidence of this phenomenon in the literature.

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Acknowledgments

The authors would like to thank Mrs. Judy Janzen-Pang for her expert technical support. NMV is a recipient of the Franklin Bracken Student Fellowship. Financial support of this research was kindly provided by the Heart and Stroke Foundation of Canada (SCP: Grant #: T-6140 and RDA: Grant #: G-14-0006260). Research equipment funding (real-time PCR) was provided by the Canada Foundation of Innovation (CFI). The use of the confocal microscopy facilities at the Queen’s University Cancer Research Centre was gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Nicole M. Ventura, Albert Y. Jin, M. Yat Tse, R. David Andrew & Stephen C. Pang

  2. Department of Medicine (Neurology), Kingston General Hospital, Kingston, ON, Canada

    Albert Y. Jin & Nichole T. Peterson

  3. Centre for Neuroscience, Queen’s University, Kingston, ON, Canada

    R. David Andrew

  4. Cancer Research Institute Queen’s University, Kingston, ON, Canada

    Jeffrey D. Mewburn

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  1. Nicole M. Ventura
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Correspondence to Albert Y. Jin or Stephen C. Pang.

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Ventura, N.M., Jin, A.Y., Tse, M.Y. et al. Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring. Mol Cell Biochem 408, 223–233 (2015). https://doi.org/10.1007/s11010-015-2498-8

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