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The Potential Effects of a Universal Plasticizer Alkylsulfonic Phenyl Ester on Dyslipidemia and Atherosclerosis

Award Number: R16GM159691
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/27/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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The Potential Effects of a Universal Plasticizer Alkylsulfonic Phenyl Ester on Dyslipidemia and Atherosclerosis - PROJECT SUMMARY/ABSTRACT Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality worldwide despite of advanced diagnosis and treatment. Our chemical environment has changed substantially in the past few decades, and recent large-scale human studies have implicated a novel link between exposure to endocrine disrupting chemicals (EDCs) and CVD. Plastics have become an essential part in modern life, and plastic pollution is a significant environmental and health concern. Plastic-associated EDCs including numerous plasticizers are produced in high volume and have been demonstrated to be associated with increased CVD risk in humans. However, the underlying mechanisms for the EDC-associated CVD are still poorly understood, making it difficult to conduct rational exposure assessment. Many plastic-associated EDCs including bisphenol A, phthalates, and phthalate substitutes have been previously identified as potent agonists of pregnane X receptor (PXR), which is a nuclear receptor activated by a variety of environmental chemicals, dietary steroids, and pharmaceutical agents. PXR functions as a xenobiotic sensor activating the expression of genes required for xenobiotic metabolism in the liver and intestine, two organs that play a central role in whole body lipid homeostasis. In addition to the role in xenobiotic metabolism, the atherogenic effect of PXR has been revealed in animal models. PXR has been shown to contribute to increased atherosclerotic development in atherosclerosis-prone low-density lipoprotein receptor-deficient (LDLR-/-) and apolipoprotein E-deficient (ApoE-/-) mouse models. Our preliminary data suggests that PXR could be activated by a non-phthalate plasticizer, alkylsulfonic phenyl ester (ASE), which is widely used for food packing, medical tubing, and children’s toys. However, it is still unclear whether ASE could cause adverse atherogenic effects through PXR signaling. The objective of this project is to assess the potential risks of ASE in dyslipidemia and atherosclerosis. The central hypothesis is that ASE promotes lipid absorption by activating PXR signaling resulting in increased plasma lipid levels and atherosclerotic development. Three specific aims are proposed by our undergraduate research team to test this hypothesis: 1) What molecular mechanisms underly PXR activation by ASE? 2) How does acute ASE exposure affect lipid uptake and lipid profiles through PXR? 3) Does chronic ASE exposure increase atherosclerotic development in atherosclerosis-prone ApoE-/- mice via PXR signaling? The proposed studies are the first to explore the cellular and molecular mechanisms by which exposure to ASE activates human PXR and increases the risk of dyslipidemia and atherosclerosis. These studies are broadly translational and will provide strong evidence to inform future CVD risk assessment for the universal plasticizer ASE as well as other environmental chemicals. Our proposed project will benefit our undergraduate students by gaining meaningful cardiovascular research experience.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $132,735 )
2026	2026	UNIVERSITY OF NEBRASKA	905 W 25TH ST	KEARNEY	NE	68849	BUFFALO	USA	Biomedical Research and Research Training	000	1	7/27/2026	NEW	$132,735
														Subtotal = $132,735

Grand Total All Awards = $132,735

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The Potential Effects of a Universal Plasticizer Alkylsulfonic Phenyl Ester on Dyslipidemia and Atherosclerosis

Award Number: R16GM159691

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/27/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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