Excessive Hypercholesterolemia in Pregnancy Impairs Later‐Life Maternal Vascular Function in Rats

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Abstract
Background: Preeclampsia is a risk factor for the development of later‐life cardiovascular disease. However, the underlying mechanisms are poorly understood. Excessive hypercholesteremia in pregnancy induces a preeclampsia‐like phenotype, but whether this also impacts maternal vascular function later in life has not been fully characterized. Methods and Results: Sprague Dawley rats received a control diet (CD) or a high‐cholesterol (HCD) diet from gestational day 6 to 20, after which maternal vascular function was assessed 3 months postpartum. Exposure to an HCD in pregnancy reduced later‐life endothelium‐dependent vasodilation in carotid arteries (−15.24±3.27%), which was mediated via prostaglandin H synthase 2. There were no differences in vasodilation between CD and HCD postpartum rats in the mesenteric arteries, coronary arteries, or aortas. Vasoconstriction to phenylephrine increased in carotid arteries (61.02±21.48%) and reduced in aortas (−23.24±6.19%) of the HCD postpartum group versus CD dams, without differences in mesenteric and coronary arteries. The increased vasoconstriction in carotid arteries was due to lower nitric oxide modulation of constriction. Moreover, carotid artery myogenic response was reduced (−37.68±10.07%) and stiffness was increased (19.67±6.21%) in the HCD postpartum rats compared with CD along with decreased elastin density (−20.85±4.52%). The impact of the HCD on vascular function did not occur in age‐matched never‐pregnant female rats. Conclusions: Excessive hypercholesterolemia in pregnancy impairs later‐life maternal vascular function in rats with varying impacts across different vascular beds. Understanding mechanisms for pregnancy‐specific excessive hypercholesterolemia provides avenues for targeted intervention strategies to reduce the burden of cardiovascular disease in women who had a complicated pregnancy.

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