PMID- 21300662
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20161125
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 57
IP  - 3
DP  - 2011 Mar
TI  - Estrogen receptor-beta signals left ventricular hypertrophy sex differences in 
      normotensive deoxycorticosterone acetate-salt mice.
PG  - 648-54
LID - 10.1161/HYPERTENSIONAHA.110.166157 [doi]
AB  - We found earlier that deoxycorticosterone acetate-salt treatment causes blood 
      pressure-independent left ventricular hypertrophy, but only in male mice. To test 
      the hypothesis that the estrogen receptor-beta (ERbeta) protects the females from left 
      ventricular hypertrophy, we treated male and female ERbeta-deficient (ERbeta(-/-)) mice 
      and their male and female littermates (wild-type [WT]) with deoxycorticosterone 
      acetate-salt and made them telemetrically normotensive with hydralazine. WT males 
      had increased (+16%) heart weight/tibia length ratios compared with WT females 
      (+7%) at 6 weeks. In ERbeta(-/-) mice, this situation was reversed. Female WT mice 
      had the greatest heart weight/tibia length ratio increases of all of the groups 
      (+23%), even greater than ERbeta(-/-) males (+10%). Echocardiography revealed 
      concentric left ventricular hypertrophy in male WT mice, whereas ERbeta(-/-) females 
      developed dilative left ventricular hypertrophy. The hypertrophic response in 
      female ERbeta(-/-) mice was accompanied by the highest degree of collagen 
      deposition, indicating maladaptive remodeling. ERbeta(+/+) females showed robust 
      protective p38 and extracellular signal-regulated kinase 1/2 signaling 
      relationships compared with other groups. Calcineurin Abeta expression and its 
      positive regulator myocyte-enriched calcineurin-interacting protein 1 were 
      increased in deoxycorticosterone acetate-salt female ERbeta(-/-) mice, yet lower 
      than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, 
      which could be blocked by estradiol and an ERbeta agonist. We conclude that a 
      functional ERbeta is essential for inducing adaptive p38 and extracellular 
      signal-regulated kinase signaling, while reducing maladaptive calcineurin 
      signaling in normotensive deoxycorticosterone acetate female mice. Our findings 
      address the possibility of sex-specific cardiovascular therapies.
FAU - Gurgen, Dennis
AU  - Gurgen D
AD  - Department of Nephrology and Intensive Care Medicine Campus Virchow-Klinikum, 
      Center forCardiovascular Research Medical Faculty, Charite  Berlin, Berlin, 
      Germany.
FAU - Hegner, Bjorn
AU  - Hegner B
FAU - Kusch, Angelika
AU  - Kusch A
FAU - Catar, Rusan
AU  - Catar R
FAU - Chaykovska, Lyubov
AU  - Chaykovska L
FAU - Hoff, Uwe
AU  - Hoff U
FAU - Gross, Volkmar
AU  - Gross V
FAU - Slowinski, Torsten
AU  - Slowinski T
FAU - da Costa Goncalves, Andrey C
AU  - da Costa Goncalves AC
FAU - Kintscher, Ulrich
AU  - Kintscher U
FAU - Gustafsson, Jan-Ake
AU  - Gustafsson JA
FAU - Luft, Friedrich C
AU  - Luft FC
FAU - Dragun, Duska
AU  - Dragun D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110207
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Mineralocorticoids)
RN  - 26NAK24LS8 (Hydralazine)
RN  - 40GP35YQ49 (Desoxycorticosterone)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Blood Pressure/drug effects
MH  - Blotting, Western
MH  - Desoxycorticosterone/*pharmacology
MH  - Echocardiography
MH  - Estrogen Receptor beta/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Hydralazine/pharmacology
MH  - Hypertrophy, Left Ventricular/chemically induced/diagnostic imaging/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mineralocorticoids/*pharmacology
MH  - Myocardium/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Sex Characteristics
MH  - Signal Transduction/drug effects
EDAT- 2011/02/09 06:00
MHDA- 2011/04/16 06:00
CRDT- 2011/02/09 06:00
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
AID - HYPERTENSIONAHA.110.166157 [pii]
AID - 10.1161/HYPERTENSIONAHA.110.166157 [doi]
PST - ppublish
SO  - Hypertension. 2011 Mar;57(3):648-54. doi: 10.1161/HYPERTENSIONAHA.110.166157. 
      Epub 2011 Feb 7.