Excessive hypercholesterolemia in pregnancy impairs the cardiovascular health of the adult female and male offspring

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Abstract
Excessive hypercholesterolemia in pregnancy is a risk factor for the development of preeclampsia, but its ensuing impact on offspring cardiovascular health remains not fully understood. In the present study, Sprague Dawley rats were fed a control or high cholesterol diet (HCD) from gestational days 6–20 (term=22 days). Female and male offspring were aged to adulthood (4 months old), and in vivo and ex vivo cardiovascular function were assessed. In female offspring, body weight gain was greater in the HCD group compared with controls after 2 months of age. Blood pressure, echocardiographic parameters, cardiac capacity to recover from an ischemic insult, and endothelium-dependent vasodilation were similar between the female groups. However, vasoconstriction to a thromboxane analog (U46619) was reduced in thoracic aortas, but not in mesenteric, coronary, or carotid arteries, from the HCD females compared with controls, and was associated with lower phosphorylated myosin phosphatase target subunit 1 (MYPT1Thr855) levels. In male offspring, body weight gain, blood pressure, and echocardiographic parameters were similar between the groups, and there was no impact of HCD on vasoconstriction to U46619 or vasodilation in mesenteric arteries, carotid arteries, or thoracic aortas. However, endothelium-dependent vasodilation was reduced in coronary arteries of HCD males compared with controls and was associated with increased reactive oxygen species levels. There was also reduced cardiac capacity of the HCD males to recover from an ischemic insult. In summary, excessive hypercholesterolemia in pregnancy impaired the cardiovascular health of adult female and male offspring, but the mechanisms and vascular beds affected were specific to each sex.

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