Exposure to plastic-associated endocrine-disrupting chemicals (EDCs) has been linked to an increased hazard of cardiovascular disease (CVD) in humans. Although, the underlying mechanisms for this association are unclear.
A new study University of California, Riverside, investigated the contribution of the pregnane X receptor (PXR) to the adverse effects of dicyclohexyl phthalate (DCHP), a widely used phthalate plasticizer, on lipid homeostasis and CVD risk factors. The study, conducted on mice models, found that a phthalate — a chemical used to make plastics more durable — led to increased plasma cholesterol levels.
In other words, exposure to plastic-associated chemicals, such as base chemical bisphenol A and phthalate plasticizers, can increase the risk of human cardiovascular disease.
Changcheng Zhou, a biomedical scientist at the University of California, Riverside, said, “We found dicyclohexyl phthalate, or DCHP, strongly binds to a receptor called the pregnane X receptor PXR. DCHP ‘turns on’ PXR in the gut, inducing the expression of key proteins required for cholesterol absorption and transport. Our experiments show that DCHP elicits high cholesterol by targeting intestinal PXR signaling.”
“To our knowledge, our study is the first to show the effects of DCHP exposure on high cholesterol and cardiovascular disease risk in mouse models. Our results provide insights and new understandings of the impact of plastic-associated chemicals on high cholesterol — or dyslipidemia — and cardiovascular disease risk.”
Scientists found that mice exposed to DCHP had in their blood higher circulating “ceramides” — a class of waxy lipid molecules associated with increased cardiovascular disease risk in humans — in a way that was PXR-dependent.
Zhou said, “This, too, points to the potentially important role of PXR in contributing to the harmful effects of plastic-associated chemicals on cardiovascular health in humans.”
The work was supported in part by the National Institute of Environmental Health Sciences or NIEHS. A recently renewed NIEHS training grant supported Hernandez to UCR. Gonzales, an undergraduate student, was a UCR honors Capstone scholar.
- Yipeng Sui, Zhaojie Meng et al. Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice. DOI: 10.1289/EHP9262