Grant Abstract: Cardiovascular protection by phpytosterols in dyslipidemic mothers and progeny

Grant Number: 5K01AT007826-05
PI Name: Rideout
Project Title: Cardiovascular protection by phpytosterols in dyslipidemic mothers and progeny

Abstract: The impact of cardiovascular diseases (CVD) on American life cannot be over-emphasized as it presents major challenges to society through direct effects on public health, well-being, and economic prosperity. Adding to the urgency of CVD as a global health issue is the rise in dyslipidemic risk factors amongst women of childbearing age due to underlying genetic and/or dietary factors. Pronounced maternal hyperlipidemia during pregnancy is a high-priority health concern as it increases maternal CVD risk and produces offspring who are predisposed to dyslipidemia and early onset atherosclerosis. As the use of lipid- lowering medication during pregnancy is contraindicated, natural lipid-lowering products should be examined as potential strategies to reduce gestational dyslipidemia. Furthermore, early exposure to dietary health promoting compounds during fetal and postnatal developmental stages may confer protection against future CVD incidence. Although there is strong scientific support that inadequate and excessive nutrient exposure during early development may underlie maladaptive health responses in adulthood, very little is known about how early exposure to health promoting bioactive compounds may protect against CVD throughout the life- course. As phytosterols are safe and effective plant-derived compounds with proven lipid-lowering efficacy, we propose to examine early phytosterol exposure with two Specific Aims: 1) examine the safety and efficacy of phytosterols in treating maternal gestational hyperlipidemia and 2) examine in utero and postnatal phytosterol exposure as a novel 'up-stream' preventative strategy to protect against CVD in adult life. We hypothesize that a maternal phytosterol-supplemented diet will reduce CVD risk factors in hyperlipidemic mothers and protect offspring against maladaptive health responses that are associated with early exposure to high fat and cholesterol. Our research objectives will be addressed in two protocols using the F1B hamster, an established model of dyslipidemia and atherosclerosis. Protocol 1 will examine the effectiveness of phytosterols in reducing cardiovascular disease risk in dyslipidemic mothers. Protocol 2 will assess in utero and postnatal phytosterol exposure as an early prevention strategy to ameliorate maladaptive dyslipidemic, arterial, and cardiac responses in adult offspring challenged with a high fat/high cholesterol diet. Research outcomes of this innovative application will address significant knowledge gaps concerning the potential efficacy and safety of early phytosterol exposure on CVD prevention for both mothers and offspring. Training activities will allow Dr. Rideout to gain advanced theoretical knowledge and technical expertise to examine arterial and cardiac health endpoints in response to early nutritional interventions. In addition, these training and research activities will be integral in preparing Dr. Rideout for a productive and independent research career in the natural products field by generating strong preliminary data for a competitive R01 application to further assess developmental nutrient programming approaches to reduce the incidence of CVD.

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