PMID- 21071029
OWN - NLM
STAT- MEDLINE
DCOM- 20110519
LR  - 20131121
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 214
IP  - 1
DP  - 2011 Jan
TI  - Protective effects of dehydroepiandrosterone on atherosclerosis in ovariectomized 
      rabbits via alleviating inflammatory injury in endothelial cells.
PG  - 47-57
LID - 10.1016/j.atherosclerosis.2010.07.043 [doi]
AB  - OBJECTIVE: The risk for atherosclerosis is increased in postmenopausal women. 
      Dehydroepiandrosterone (DHEA) is postulated to have anti-atherogenic properties, 
      but the mechanism remains unclear. The aim of this study was to elucidate the 
      protective effect of DHEA on atherosclerosis in ovariectomized rabbits. METHODS: 
      The lipid status and atherosclerotic lesions were examined in vivo in 
      ovariectomized rabbits. The effects of DHEA on expression of inflammatory 
      molecules were evaluated in vitro, such as nitric oxide (NO), malondialdehyde 
      (MDA), monocyte chemoattractant protein-1 (MCP-1), adhesion molecules (ICAM-1, 
      VCAM-1 and E-selectin) in the human umbilical vein endothelial cells (HUVECs) 
      injured by oxidized low-density lipoproteins (ox-LDL). The adhesion of the 
      monocytic U937 cells to HUVECs was treated with supernatants of ox-LDL treated 
      HUVECs with or without DHEA, and then the expressions of CCR2, LFA-1, VLA-4 were 
      analyzed in U937 cells. The HUVECs with or without LPS treatment were then 
      treated with DHEA, and NF-kappaB activity was measured by luciferase activity. 
      RESULTS: DHEA administration alleviates efficiently the early pathologic damage 
      of atherosclerosis, increases the serum NO level, and up-regulates the 
      endothelial cell estrogen receptor (ER) expression of ovariectomized rabbits. 
      DHEA in vitro significantly promotes NO synthesis, suppresses MDA and MCP-1 
      secretion of endothelial cells, and decreases ICAM-1, VCAM-1 and E-selectin 
      expression in HUVECs; neither selective ERalpha antagonist 
      (methyl-piperidino-pyrazole, MPP) nor ERbeta antagonist (R,R-tetrahydrochrysene, 
      R,RTHC) can abolish these effects. Furthermore, DHEA reduces CCR2, LFA-1 and 
      VLA-4 expression in U937 cells, which in turn inhibits the adherence of monocytes 
      to the injured endothelial cells. DHEA significantly decreased the LPS-induced 
      NF-kappaB transcription. CONCLUSIONS: Our findings suggest that DHEA can alleviate 
      inflammation in endothelial cells. The effects of DHEA on endothelial cells are 
      independent of ERalpha or ERbeta pathway, but at least in part, through suppression of 
      NF-kappaB activity, which protects from atherosclerosis triggered by monocyte 
      adherence.
CI  - Copyright A(c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Wang, Ling
AU  - Wang L
AD  - Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical 
      College, Shanghai 200011, China.
FAU - Hao, Qun
AU  - Hao Q
FAU - Wang, Yu-Dong
AU  - Wang YD
FAU - Wang, Wen-Jun
AU  - Wang WJ
FAU - Li, Da-Jin
AU  - Li DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100803
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Chemokine CCL2)
RN  - 0 (E-Selectin)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4Y8F71G49Q (Malondialdehyde)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*drug therapy/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Dehydroepiandrosterone/*therapeutic use
MH  - E-Selectin/metabolism
MH  - Endothelial Cells/*cytology/drug effects
MH  - Female
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Lipid Metabolism
MH  - Malondialdehyde/metabolism
MH  - Nitric Oxide/metabolism
MH  - Ovariectomy/methods
MH  - Rabbits
MH  - Risk
MH  - U937 Cells
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2010/11/13 06:00
MHDA- 2011/05/20 06:00
CRDT- 2010/11/13 06:00
PHST- 2009/09/03 00:00 [received]
PHST- 2010/06/28 00:00 [revised]
PHST- 2010/07/21 00:00 [accepted]
PHST- 2010/11/13 06:00 [entrez]
PHST- 2010/11/13 06:00 [pubmed]
PHST- 2011/05/20 06:00 [medline]
AID - S0021-9150(10)00588-5 [pii]
AID - 10.1016/j.atherosclerosis.2010.07.043 [doi]
PST - ppublish
SO  - Atherosclerosis. 2011 Jan;214(1):47-57. doi: 
      10.1016/j.atherosclerosis.2010.07.043. Epub 2010 Aug 3.