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Developmental origins of pregnancy-induced cardiac changes: establishment of a novel model using the atrial natriuretic peptide gene-disrupted mice

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Abstract

Pregnancy evokes many challenges on the maternal cardiovascular system that may unmask predispositions for future disease. This is particularly evident for women who develop pregnancy-related disorders, for example, pre-eclampsia and gestational diabetes or hypertension. Such pregnancy-related syndromes increase the risk for cardiovascular disease (CVD) postpartum. As a result, pregnancy has been termed as a cardiovascular stress test and an indicator or marker to predict the development of CVD later in life. In addition, pregnancy-related disorders impact the development of offspring also placing them at a higher risk for disease. Utilizing pregnancy as a physiological stressor, the current investigation sought to determine whether the cardiovascular system of offspring exposed to gestational hypertension in utero would respond adversely to the stress of pregnancy. Heterozygous atrial natriuretic peptide gene-disrupted (ANP+/−) offspring were generated by either crossing male wildtype ANP+/+ with female knockout ANP−/− to produce ANP+/−KO mice or crossing female wildtype ANP+/+ with male knockout ANP−/− to produce ANP+/−WT mice. To study the cardiovascular stress induced by pregnancy, female ANP+/−WT and ANP+/−KO mice were mated with male wildtype ANP+/+ mice to initiate pregnancy. Cardiac size and molecular expression of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) were compared between offspring groups. Our data demonstrate that gestational hypertension and lack of maternal ANP did not significantly impact the progression and regression of pregnancy-induced cardiac hypertrophy over gestation and postpartum in ANP+/− offspring. Additionally, the molecular cardiac expression of the RAS and NPS did not differ between offspring groups. Future investigation should assess potential differences in cardiac function and the impact of fetal-programming on offspring cardiovascular adaptations during pregnancy in more severe models of pregnancy-related hypertensive syndrome such as angiotensin II or isoproterenol infusion.

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Funding

Heart and Stroke Foundation of Canada provided funding to SCP (Grant #: T-6140) and to RDA (Grant #: G-14-0006260). N.M.V. was the recipient of the R.S. McLaughlin Fellowship, Queen’s University.

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  1. Nicole M. Ventura

    Present address: Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Room 1/54 Strathcona Anatomy Building, 3640 University St., Montreal, QC, H3A 0C7, Canada

Authors and Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen’s University, Botterell Hall – 18 Stuart St., Kingston, ON, K7L 3N6, Canada

    Nicole M. Ventura, Terry Y. Li, M. Yat Tse, Logan Richard, Chandrakant Tayade, Albert Y. Jin, R. David Andrew & Stephen C. Pang

  2. Department of Medicine (Neurology), Kingston General Hospital, 76 Stuart St. Kingston, Kingston, ON, K7L 2V7, Canada

    Albert Y. Jin

  3. Department of Biomedical and Molecular Sciences, Queen’s University, Rm 850 Botterell Hall, 18 Stuart St., Kingston, ON, K7L 3N6, Canada

    Stephen C. Pang

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  1. Nicole M. Ventura
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Correspondence to Stephen C. Pang.

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Ventura, N.M., Li, T.Y., Tse, M.Y. et al. Developmental origins of pregnancy-induced cardiac changes: establishment of a novel model using the atrial natriuretic peptide gene-disrupted mice. Mol Cell Biochem 449, 227–236 (2018). https://doi.org/10.1007/s11010-018-3359-z

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