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 language | English |
|---|---|
| Pages (from-to) | 181-190 |
| Number of pages | 10 |
| Journal | Archives of Toxicology |
| Volume | 90 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 Jan 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Toxicology
- Health, Toxicology and Mutagenesis
Cite this
}
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 journal › Article
TY - JOUR
T1 - Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice
AU - Zhao, Jin Feng
AU - Hsiao, Sheng Huang
AU - Hsu, Ming Hua
AU - Pao, Kuan Chuan
AU - Kou, Yu Ru
AU - Shyue, Song Kun
AU - Lee, Tzong Shyuan
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84955347915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955347915&partnerID=8YFLogxK
U2 - 10.1007/s00204-014-1377-5
DO - 10.1007/s00204-014-1377-5
M3 - Article
C2 - 25270622
AN - SCOPUS:84955347915
VL - 90
SP - 181
EP - 190
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
SN - 0003-9446
IS - 1
ER -