TY - JOUR
T1 - Treatment with an estrogen receptor-beta-selective agonist is cardioprotective
AU - Nikolic, Ivana
AU - Liu, Dianxin
AU - Bell, Jamie A.
AU - Collins, Jennifer
AU - Steenbergen, Charles
AU - Murphy, Elizabeth
N1 - Funding Information:
We thank Danica Ducharme and the NIEHS microarray group for performing the microarray experiment. This research was supported in part by the Intramural Program of the NIH (NIEHS and NHLBI). CS was supported by HL39752.
PY - 2007/4
Y1 - 2007/4
N2 - This study was designed to investigate whether treatment with an estrogen receptor-beta (ER-β)-selective agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN) can provide cardioprotection in female mice lacking endogenous estrogen. To study the effect of ER-β stimulation in ischemia-reperfusion injury, we treated ovariectomized (ovx) female mice with 0.1 mg/kg/day of 17β-estradiol, 0.8 mg/kg/day of DPN, or vehicle for 2 weeks. Isolated hearts were Langendorff perfused for 25 min prior to a 1-min treatment with isoproterenol, followed by 20 min of normothermic global ischemia and 40 min of reperfusion. Left ventricular developed pressure (LVDP) and heart rate were measured. Recovery of function at the end of 40 min of reperfusion was expressed as a percentage of pre-ischemic rate pressure product (RPP = LVDP × heart rate). Hearts from ovx female mice had a significantly lower recovery of LVDP than the hearts from intact female mice (12.4 ± 1.6% vs. 19.6 ± 1.6%, p < 0.05, respectively). Furthermore, hearts from ovx female mice treated with DPN exhibited significantly better functional recovery than hearts from either vehicle-treated ovx female mice (20.1 ± 2.2% vs. 12.4 ± 1.6%, p < 0.05, respectively) or wild type male mice (20.1 ± 2.2% vs. 6.4 ± 0.6%, p < 0.05, respectively). DPN did not increase uterine weight in ovx females compared to vehicle treatment. Gene profiling showed that treatment with DPN resulted in upregulation of a number of protective genes such as heat shock protein 70, the antiapoptotic protein, growth arrest and DNA damage 45 β, and cyclooxygenase 2.
AB - This study was designed to investigate whether treatment with an estrogen receptor-beta (ER-β)-selective agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN) can provide cardioprotection in female mice lacking endogenous estrogen. To study the effect of ER-β stimulation in ischemia-reperfusion injury, we treated ovariectomized (ovx) female mice with 0.1 mg/kg/day of 17β-estradiol, 0.8 mg/kg/day of DPN, or vehicle for 2 weeks. Isolated hearts were Langendorff perfused for 25 min prior to a 1-min treatment with isoproterenol, followed by 20 min of normothermic global ischemia and 40 min of reperfusion. Left ventricular developed pressure (LVDP) and heart rate were measured. Recovery of function at the end of 40 min of reperfusion was expressed as a percentage of pre-ischemic rate pressure product (RPP = LVDP × heart rate). Hearts from ovx female mice had a significantly lower recovery of LVDP than the hearts from intact female mice (12.4 ± 1.6% vs. 19.6 ± 1.6%, p < 0.05, respectively). Furthermore, hearts from ovx female mice treated with DPN exhibited significantly better functional recovery than hearts from either vehicle-treated ovx female mice (20.1 ± 2.2% vs. 12.4 ± 1.6%, p < 0.05, respectively) or wild type male mice (20.1 ± 2.2% vs. 6.4 ± 0.6%, p < 0.05, respectively). DPN did not increase uterine weight in ovx females compared to vehicle treatment. Gene profiling showed that treatment with DPN resulted in upregulation of a number of protective genes such as heat shock protein 70, the antiapoptotic protein, growth arrest and DNA damage 45 β, and cyclooxygenase 2.
KW - Cardioprotection
KW - Estrogen
KW - Heart
KW - Ischemia
UR - http://www.scopus.com/inward/record.url?scp=34047154988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047154988&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2007.01.014
DO - 10.1016/j.yjmcc.2007.01.014
M3 - Article
C2 - 17362982
AN - SCOPUS:34047154988
SN - 0022-2828
VL - 42
SP - 769
EP - 780
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 4
ER -