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. !!

Public Health Relevance

Gestational dyslipidemia is a high priority health issue as it increases maternal cardiovascular (CVD) risk and produces offspring predisposed to hyperlipidemia and atherosclerosis. This application will examine phytosterol intervention from pre-pregnancy to offspring weaning on CVD risk in both mothers and progeny.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZAT1)
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Alekel, D Lee
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State University of New York at Buffalo
Other Health Professions
Sch Allied Health Professions
United States
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Dumolt, Jerad H; Radhakrishnan, Sandhya K; Moghadasian, Mohammed H et al. (2018) Maternal hypercholesterolemia enhances oxysterol concentration in mothers and newly weaned offspring but is attenuated by maternal phytosterol supplementation. J Nutr Biochem 52:10-17
Dumolt, Jerad H; Browne, Richard W; Patel, Mulchand S et al. (2018) Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny. Mol Nutr Food Res :e1800563
Jones, Peter J H; Shamloo, Maryam; MacKay, Dylan S et al. (2018) Progress and perspectives in plant sterol and plant stanol research. Nutr Rev 76:725-746
Juritsch, Anthony; Tsai, Yi-Ting; Patel, Mulchand S et al. (2017) Transcriptional control of enterohepatic lipid regulatory targets in response to early cholesterol and phytosterol exposure in apoE-/- mice. BMC Res Notes 10:529
Dumolt, Jerad H; Rideout, Todd C (2017) The Lipid-lowering Effects and Associated Mechanisms of Dietary Phytosterol Supplementation. Curr Pharm Des 23:5077-5085
Liu, Jie; Iqbal, Aadil; Raslawsky, Amy et al. (2016) Influence of maternal hypercholesterolemia and phytosterol intervention during gestation and lactation on dyslipidemia and hepatic lipid metabolism in offspring of Syrian golden hamsters. Mol Nutr Food Res 60:2151-2160
Rideout, Todd C; Carrier, Bradley; Wen, Shin et al. (2016) Complementary Cholesterol-Lowering Response of a Phytosterol/?-Lipoic Acid Combination in Obese Zucker Rats. J Diet Suppl 13:283-99
Rideout, Todd C; Marinangeli, Christopher P F; Harding, Scott V (2015) Triglyceride-Lowering Response to Plant Sterol and Stanol Consumption. J AOAC Int 98:707-15
Rideout, Todd C; Movsesian, Cheryl; Tsai, Yi-Ting et al. (2015) Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice. J Nutr 145:1728-34
Rideout, Todd C; Ramprasath, Vanu; Griffin, John D et al. (2014) Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters. Lipids Health Dis 13:5