The role of estrogen receptors alpha and beta in atherosclerotic lesion calcification in apolipoprotein e-null mice

L. McRobb, E. Liong, J. Tan, A. Heather

Research output: Contribution to journalMeeting abstract


Objectives: We previously observed increases in lesion calcification in the aortic sinus of ApoEnull
mice treated with testosterone (T) associated with suppression of estrogen receptor (ER)
alpha but not ERbeta expression. Our objective was to determine whether lesion calcification is
induced by ERalpha suppression or by alterations to the cellular ratio of ERbeta/ERalpha.

Methods: 34 week old intact male ApoE-null mice were treated by subdermal implant with T, or
biweekly with ERalpha/ERbeta antagonist, ICI 172380 (2mg/0.1mL corn oil), or ERalpha
antagonist, Methyl-piperidino-pyrazole (MPP) (3mg/0.1mL corn oil) by intraperitoneal injection,
for 8 weeks. Plaque and calcified areas were quantified in the aortic sinus.

Results: Suppression of ERalpha expression by supraphysiological T treatment increased the
frequency of calcified lesions (77% vs. 36%, P=0.045) as well as mean calcified area (3-fold,
P=0.04). Specific blockade of ERalpha with MPP at physiologic T levels also increased the
frequency of calcified lesions (80% vs. 36%, P=0.044) and showed a trend toward increased
calcified area (3-fold, P=0.068). In contrast, simultaneous blockade of ERalpha and ERbeta had
no effect on calcification compared to vehicle controls and significantly decreased the frequency
of calcified lesions (27% vs. 80%, P=0.016) and calcified area (15-fold, P=0.0028) relative to
MPP-treated mice.

Conclusions: ERalpha antagonism increases lesion calcification in the aortic sinus of intact
male ApoE-null mice but only in the presence of active ERbeta. We conclude that ERbeta and
the ERalpha/beta ratio is critical for lesion calcification in this model.
Original languageEnglish
Article numberP168
Pages (from-to)1-1
Number of pages1
JournalAtherosclerosis Supplements
Issue number2
Publication statusPublished - Jun 2009
Externally publishedYes

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