Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice
| Autor: | Song-Kun Shyue, Tzong Shyuan Lee, Ming Hua Hsu, Jin Feng Zhao, Sheng Huang Hsiao, Yu Ru Kou, Kuan Chuan Pao |
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| Rok vydání: | 2014 |
| Předmět: |
Male
0301 basic medicine Apolipoprotein E endocrine system medicine.medical_specialty Time Factors Apolipoprotein B Adipose Tissue White Health Toxicology and Mutagenesis Inflammation Toxicology Risk Assessment Cell Line 03 medical and health sciences chemistry.chemical_compound Apolipoproteins E Plasticizers Diethylhexyl Phthalate Internal medicine medicine Animals Humans Genetic Predisposition to Disease Liver X receptor Adiposity Mice Knockout biology Cholesterol Macrophages Phthalate Endothelial Cells General Medicine Atherosclerosis Lipoproteins LDL Disease Models Animal Phenotype 030104 developmental biology Endocrinology Liver chemistry LDL receptor Disease Progression biology.protein lipids (amino acids peptides and proteins) Inflammation Mediators medicine.symptom Lipoprotein |
| Zdroj: | Archives of Toxicology. 90:181-190 |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | Di-(2-ethylhexyl) phthalate (DEHP) is associated with atherosclerosis-related cardiovascular disease complications, but we lack direct evidence of its unfavorable effect on atherogenesis. In this study, we aimed to clarify in vivo and in vitro the contribution of DEHP to the development of atherosclerosis and its underlying mechanisms. Apolipoprotein E-deficient (apoE(-/-)) mice chronically treated with DEHP for 4 weeks showed exacerbated hyperlipidemia, systemic inflammation, and atherosclerosis. In addition, DEHP promoted low-density lipoprotein (LDL) oxidation, which led to inflammation in endothelial cells as evidenced by increased protein expression of pro-inflammatory mediators. Furthermore, chronic DEHP treatment increased hepatic cholesterol accumulation by downregulating the protein expression of key regulators in cholesterol clearance including LDL receptor, cholesterol 7α-hydrolase, ATP-binding cassette transporter G5 and G8, and liver X receptor α. Moreover, the adiposity and inflammation of white adipose tissues were promoted in DEHP-treated apoE(-/-) mice. In conclusion, DEHP may disturb cholesterol homeostasis and deregulate the inflammatory response, thus leading to accelerated atherosclerosis. |
| Databáze: | OpenAIRE |
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