Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice

Jin Feng Zhao, Sheng Huang Hsiao, Ming Hua Hsu, Kuan Chuan Pao, Yu Ru Kou, Song Kun Shyue, Tzong Shyuan Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalArchives of Toxicology
Volume90
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Apolipoproteins E
Atherosclerosis
Cholesterol
Inflammation
White Adipose Tissue
ATP-Binding Cassette Transporters
LDL Receptors
Endothelial cells
Adiposity
Hydrolases
phthalic acid
Hyperlipidemias
LDL Lipoproteins
Liver
LDL Cholesterol
Proteins
Homeostasis
Cardiovascular Diseases
Down-Regulation
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Zhao, Jin Feng ; Hsiao, Sheng Huang ; Hsu, Ming Hua ; Pao, Kuan Chuan ; Kou, Yu Ru ; Shyue, Song Kun ; Lee, Tzong Shyuan. / Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice. In: Archives of Toxicology. 2016 ; Vol. 90, No. 1. pp. 181-190.
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Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice. / Zhao, Jin Feng; Hsiao, Sheng Huang; Hsu, Ming Hua; Pao, Kuan Chuan; Kou, Yu Ru; Shyue, Song Kun; Lee, Tzong Shyuan.

In: Archives of Toxicology, Vol. 90, No. 1, 01.01.2016, p. 181-190.

Research output: Contribution to journalArticle

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AU - Hsiao, Sheng Huang

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AU - Kou, Yu Ru

AU - Shyue, Song Kun

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AB - 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.

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