PMID- 22099601
OWN - NLM
STAT- MEDLINE
DCOM- 20120430
LR  - 20211021
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 173
IP  - 1
DP  - 2012 Mar
TI  - The role of estrogen receptor alpha and beta in regulating vascular smooth muscle cell 
      proliferation is based on sex.
PG  - e1-10
LID - 10.1016/j.jss.2011.09.021 [doi]
AB  - BACKGROUND: We previously demonstrated that vascular smooth muscle cells (VSMC) 
      proliferation and development of neointimal hyperplasia as well as the ability of 
      nitric oxide (NO) to inhibit these processes is dependent on sex and hormone 
      status. The aim of this study was to evaluate the role of estrogen receptor (ER) 
      in mediating proliferation in male and female VSMC. MATERIALS AND METHODS: 
      Proliferation was assessed in primary rat aortic male and female VSMC using 
      (3)H-thymidine incorporation in the presence or absence of ER alpha (alpha) inhibitor 
      methyl-piperidino-pyrazole, the ER beta (beta) inhibitor 
      (R,R)-5,11-Diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol, the combined ERalphabeta 
      inhibitor ICI 182,780, and/or the NO donor DETA/NO. Proliferation was also 
      assessed in primary aortic mouse VSMC harvested from wildtype (WT), ERalpha knockout 
      (ERalpha KO), and ERbeta knockout (ERbeta KO) mice in the presence or absence of DETA/NO 
      and the ERalpha, ERbeta, and ERalphabeta inhibitors. Protein levels were assessed using Western 
      blot analysis. RESULTS: Protein expression of ERalpha and ERbeta was present and equal 
      in male and female VSMC, and did not change after exposure to NO. Inhibition of 
      either ERalpha or ERbeta had no effect on VSMC proliferation in the presence or absence 
      of NO in either sex. However, inhibition of ERalphabeta in rat VSMC mitigated 
      NO-mediated inhibition in female but not male VSMC (P < 0.05). Evaluation of 
      proliferation in the knockout mice revealed distinct patterns. Male ERalphaKO and 
      ERbetaKO VSMC proliferated faster than male WT VSMC (P < 0.05). Female ERbetaKO 
      proliferated faster than female WT VSMC (P < 0.05), but female ERalphaKO VSMC 
      proliferated slower than female WT VSMC (P < 0.05). Last, we evaluated the effect 
      of combined inhibition of ERalpha and ERbeta in these knockout strains. Combined ERalphabeta 
      inhibition abrogated NO-mediated inhibition of VSMC proliferation in female WT 
      and knockout VSMC (P < 0.05), but not in male VSMC. CONCLUSIONS: These data 
      clearly demonstrate a role for the ER in mediating VSMC proliferation in both 
      sexes. However, these data suggest that the antiproliferative effects of NO may 
      be regulated by the ER in females but not males.
CI  - Published by Elsevier Inc.
FAU - Hogg, Melissa E
AU  - Hogg ME
AD  - Division of Vascular Surgery, Northwestern University Feinberg School of 
      Medicine, Chicago, Illinois 60611, USA.
FAU - Vavra, Ashley K
AU  - Vavra AK
FAU - Banerjee, Monisha N
AU  - Banerjee MN
FAU - Martinez, Janet
AU  - Martinez J
FAU - Jiang, Qun
AU  - Jiang Q
FAU - Keefer, Larry K
AU  - Keefer LK
FAU - Chambon, Pierre
AU  - Chambon P
FAU - Kibbe, Melina R
AU  - Kibbe MR
LA  - eng
GR  - K08HL084203/HL/NHLBI NIH HHS/United States
GR  - UL1 RR025741/RR/NCRR NIH HHS/United States
GR  - K08 HL084203-05/HL/NHLBI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - N01CO12400/CA/NCI NIH HHS/United States
GR  - K08 HL084203/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111008
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
CIN - J Surg Res. 2013 Mar;180(1):45-6. PMID: 22316676
MH  - Animals
MH  - *Cell Proliferation/drug effects
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogen Receptor alpha/antagonists & inhibitors/genetics/*physiology
MH  - Estrogen Receptor beta/antagonists & inhibitors/genetics/*physiology
MH  - Female
MH  - Fulvestrant
MH  - Hyperplasia/chemically induced/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Muscle, Smooth, Vascular/*cytology/drug effects/physiology
MH  - Neointima/chemically induced/pathology
MH  - Nitric Oxide/adverse effects/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sex Characteristics
MH  - Signal Transduction
PMC - PMC3286876
MID - NIHMS339848
EDAT- 2011/11/22 06:00
MHDA- 2012/05/01 06:00
PMCR- 2013/03/01
CRDT- 2011/11/22 06:00
PHST- 2011/05/04 00:00 [received]
PHST- 2011/08/26 00:00 [revised]
PHST- 2011/09/13 00:00 [accepted]
PHST- 2011/11/22 06:00 [entrez]
PHST- 2011/11/22 06:00 [pubmed]
PHST- 2012/05/01 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - S0022-4804(11)00750-5 [pii]
AID - 10.1016/j.jss.2011.09.021 [doi]
PST - ppublish
SO  - J Surg Res. 2012 Mar;173(1):e1-10. doi: 10.1016/j.jss.2011.09.021. Epub 2011 Oct 
      8.