PMID- 18367192
OWN - NLM
STAT- MEDLINE
DCOM- 20100126
LR  - 20211020
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 201
IP  - 1
DP  - 2008 Nov
TI  - Selective estrogen receptor modulation influences atherosclerotic plaque 
      composition in a rabbit menopause model.
PG  - 76-84
LID - 10.1016/j.atherosclerosis.2008.01.017 [doi]
AB  - OBJECTIVE: Osteoporosis trials suggest raloxifene decreased cardiovascular events 
      in women with pre-existing atherosclerosis. We assessed the hypothesis that 
      selective estrogen receptor modulation induces plaque stability in "menopausal" 
      animals. METHODS AND RESULTS: Atherosclerosis was induced in 42 ovariectomized 
      New Zealand white rabbits by cholesterol feeding and mechanical injury. Animals 
      were imaged by magnetic resonance imaging (MRI) for baseline atherosclerosis, and 
      randomized to control (OVX (ovariectomized control group), n=12), raloxifene 
      35-60 mg/kg/day by diet admixture (RLX (raloxifene therapy group), n=24), or 
      immediate sacrifice (n=6) for immunohistopathologic correlation of MRI. Six 
      months later, rabbits underwent repeat MRI then sacrifice for micro-computed 
      tomography (microCT) and molecular analysis. Unlike OVX, RLX reduced atheroma 
      volume. Analysis for lesion inflammation revealed reductions in COX-2 
      (cyclooxygenase-2), MMP-1 (matrix metalloproteinase-1), MCP-1 (monocyte 
      chemoattractant protein-1) expression and macrophage infiltration in RLX versus 
      OVX with concomitant upregulation of estrogen receptor alpha (ERalpha). microCT 
      showed similar total vascular calcification between groups, but calcifications in 
      RLX were less nodular with better radial organization (mean calcific arc angle 
      63+/-7 degrees versus 33+/-6 degrees in OVX), the predicted result of a 53% 
      increase in BMP-2 (bone-morphogenetic protein-2). CONCLUSIONS: Raloxifene 
      treatment results in reduced lesion volume, enhanced mechanical stability of 
      vascular calcification, and less inflamed lesions characterized by less 
      macrophage infiltration and reduced COX-2, MMP-1 and MCP-1 expression.
FAU - Choi, Brian G
AU  - Choi BG
AD  - Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New 
      York, NY, USA.
FAU - Vilahur, Gemma
AU  - Vilahur G
FAU - Zafar, M Urooj
AU  - Zafar MU
FAU - Cardoso, Luis
AU  - Cardoso L
FAU - Yadegar, Daniel
AU  - Yadegar D
FAU - Ibanez, Borja
AU  - Ibanez B
FAU - Tunstead, James
AU  - Tunstead J
FAU - Viles-Gonzalez, Juan F
AU  - Viles-Gonzalez JF
FAU - Schaffler, Mitchell B
AU  - Schaffler MB
FAU - Fuster, Valentin
AU  - Fuster V
FAU - Badimon, Juan J
AU  - Badimon JJ
LA  - eng
GR  - HL54469/HL/NHLBI NIH HHS/United States
GR  - T32 HL007824-10/HL/NHLBI NIH HHS/United States
GR  - R01 HL071264-03/HL/NHLBI NIH HHS/United States
GR  - T32 HL007824/HL/NHLBI NIH HHS/United States
GR  - R01 HL071264/HL/NHLBI NIH HHS/United States
GR  - P50 HL054469-099005/HL/NHLBI NIH HHS/United States
GR  - P50 HL054469/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080221
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Chemokine CCL2)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 4F86W47BR6 (Raloxifene Hydrochloride)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*drug therapy/metabolism/*pathology
MH  - Chemokine CCL2/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Magnetic Resonance Imaging
MH  - Matrix Metalloproteinase 1/metabolism
MH  - *Menopause
MH  - Osteoporosis/*drug therapy/metabolism/pathology
MH  - Ovariectomy
MH  - Rabbits
MH  - Raloxifene Hydrochloride/*therapeutic use
MH  - Selective Estrogen Receptor Modulators/*therapeutic use
PMC - PMC3387929
MID - NIHMS78385
EDAT- 2008/03/28 09:00
MHDA- 2010/01/27 06:00
PMCR- 2012/07/02
CRDT- 2008/03/28 09:00
PHST- 2007/10/23 00:00 [received]
PHST- 2007/12/23 00:00 [revised]
PHST- 2008/01/23 00:00 [accepted]
PHST- 2008/03/28 09:00 [pubmed]
PHST- 2010/01/27 06:00 [medline]
PHST- 2008/03/28 09:00 [entrez]
PHST- 2012/07/02 00:00 [pmc-release]
AID - S0021-9150(08)00059-2 [pii]
AID - 10.1016/j.atherosclerosis.2008.01.017 [doi]
PST - ppublish
SO  - Atherosclerosis. 2008 Nov;201(1):76-84. doi: 
      10.1016/j.atherosclerosis.2008.01.017. Epub 2008 Feb 21.