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

被引:44
作者
Zhao, Jin-Feng [1 ]
Hsiao, Sheng-Huang [2 ]
Hsu, Ming-Hua [3 ]
Pao, Kuan-Chuan [3 ]
Kou, Yu Ru [1 ]
Shyue, Song-Kun [4 ]
Lee, Tzong-Shyuan [1 ]
机构
[1] Natl Yang Ming Univ, Sch Med, Dept Physiol, Taipei 11221, Taiwan
[2] Ren Ai Taipei City Hosp, Dept Surg, Taipei 10629, Taiwan
[3] Natl Tsing Hua Univ, Nucl Sci & Technol Dev Ctr, Hsinchu 30013, Taiwan
[4] Acad Sinica, Inst Biomed Sci, Div Cardiovasc, Taipei 11529, Taiwan
关键词
DEHP; Atherosclerosis; Cholesterol metabolism; Inflammation; Obesity; DI-2-ETHYLHEXYL PHTHALATE; INFLAMMATORY MOLECULES; HEMODIALYSIS-PATIENTS; HEALTH-RISKS; BISPHENOL-A; EXPOSURE; MECHANISMS; CHOLESTEROL; DISEASE; LIVER;
D O I
10.1007/s00204-014-1377-5
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 7 alpha-hydrolase, ATP-binding cassette transporter G5 and G8, and liver X receptor alpha. 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.
引用
收藏
页码:181 / 190
页数:10
相关论文
共 51 条
[1]   ATHEROSCLEROSIS - BASIC MECHANISMS - OXIDATION, INFLAMMATION, AND GENETICS [J].
BERLINER, JA ;
NAVAB, M ;
FOGELMAN, AM ;
FRANK, JS ;
DEMER, LL ;
EDWARDS, PA ;
WATSON, AD ;
LUSIS, AJ .
CIRCULATION, 1995, 91 (09) :2488-2496
[2]   MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES MONOCYTE ENDOTHELIAL INTERACTIONS [J].
BERLINER, JA ;
TERRITO, MC ;
SEVANIAN, A ;
RAMIN, S ;
KIM, JA ;
BAMSHAD, B ;
ESTERSON, M ;
FOGELMAN, AM .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) :1260-1266
[3]   The lipid-laden foam cell: an elusive target for therapeutic intervention [J].
Brewer, HB .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (06) :703-705
[4]   Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis [J].
Bunderson, M ;
Brooks, DM ;
Walker, DL ;
Rosenfeld, ME ;
Coffin, JD ;
Beall, HD .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2004, 201 (01) :32-39
[5]   MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN INDUCES MONOCYTE CHEMOTACTIC PROTEIN-1 IN HUMAN ENDOTHELIAL-CELLS AND SMOOTH-MUSCLE CELLS [J].
CUSHING, SD ;
BERLINER, JA ;
VALENTE, AJ ;
TERRITO, MC ;
NAVAB, M ;
PARHAMI, F ;
GERRITY, R ;
SCHWARTZ, CJ ;
FOGELMAN, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (13) :5134-5138
[6]   Targeted complement inhibition as a promising strategy for preventing inflammatory complications in hemodialysis [J].
DeAngelis, Robert A. ;
Reis, Edimara S. ;
Ricklin, Daniel ;
Lambris, John D. .
IMMUNOBIOLOGY, 2012, 217 (11) :1097-1105
[7]   Exposure of hemodialysis patients to di-2-ethylhexyl phthalate [J].
Faouzi, MA ;
Dine, T ;
Gressier, B ;
Kambia, K ;
Luyckx, M ;
Pagniez, D ;
Brunet, C ;
Cazin, M ;
Belabed, A ;
Cazin, JC .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 180 (01) :113-121
[8]   Clinical epidemiology of cardiovascular disease in chronic renal disease [J].
Foley, RN ;
Parfrey, PS ;
Sarnak, MJ .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1998, 32 (05) :S112-S119
[9]   Immune and Inflammatory Mechanisms of Atherosclerosis [J].
Galkina, Elena ;
Ley, Klaus .
ANNUAL REVIEW OF IMMUNOLOGY, 2009, 27 :165-197
[10]   Atherosclerosis: The road ahead [J].
Glass, CK ;
Witztum, JL .
CELL, 2001, 104 (04) :503-516