PMID- 30571375
OWN - NLM
STAT- MEDLINE
DCOM- 20191211
LR  - 20210109
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 7
IP  - 21
DP  - 2018 Nov 6
TI  - Estradiol Treatment Initiated Early After Ovariectomy Regulates Myocardial Gene 
      Expression and Inhibits Diastolic Dysfunction in Female Cynomolgus Monkeys: 
      Potential Roles for Calcium Homeostasis and Extracellular Matrix Remodeling.
PG  - e009769
LID - 10.1161/JAHA.118.009769 [doi]
LID - e009769
AB  - Background Left ventricular ( LV ) diastolic dysfunction often precedes heart 
      failure with preserved ejection fraction, the dominant form of heart failure in 
      postmenopausal women. The objective of this study was to determine the effect of 
      oral estradiol treatment initiated early after ovariectomy on LV function and 
      myocardial gene expression in female cynomolgus macaques. Methods and Results 
      Monkeys were ovariectomized and randomized to receive placebo (control) or oral 
      estradiol at a human-equivalent dose of 1 mg/day for 8 months. Monkeys then 
      underwent conventional and tissue Doppler imaging to assess cardiac function, 
      followed by transcriptomic and histomorphometric analyses of LV myocardium. Age, 
      body weight, blood pressure, and heart rate were similar between groups. 
      Echocardiographic mitral early and late inflow velocities, mitral annular 
      velocities, and mitral E deceleration slope were higher in estradiol monkeys (all 
      P<0.05), despite similar estimated LV filling pressure. MCP1 (monocyte 
      chemoattractant protein 1) and LV collagen staining were lower in estradiol 
      animals ( P<0.05). Microarray analysis revealed differential myocardial 
      expression of 40 genes (>1.2-fold change; false discovery rate, P<0.05) in 
      estradiol animals relative to controls, which implicated pathways associated with 
      better calcium ion homeostasis and muscle contraction and lower extracellular 
      matrix deposition ( P<0.05). Conclusions Estradiol treatment initiated soon after 
      ovariectomy resulted in enhanced LV diastolic function, and altered myocardial 
      gene expression towards decreased extracellular matrix deposition, improved 
      myocardial contraction, and calcium homeostasis, suggesting that estradiol 
      directly or indirectly modulates the myocardial transcriptome to preserve 
      cardiovascular function.
FAU - Michalson, Kristofer T
AU  - Michalson KT
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Groban, Leanne
AU  - Groban L
AD  - 2 Department of Anesthesiology Wake Forest University School of Medicine 
      Winston-Salem NC.
FAU - Howard, Timothy D
AU  - Howard TD
AD  - 3 Department of Biochemistry Wake Forest University School of Medicine 
      Winston-Salem NC.
FAU - Shively, Carol A
AU  - Shively CA
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Sophonsritsuk, Areepan
AU  - Sophonsritsuk A
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Appt, Susan E
AU  - Appt SE
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Cline, J Mark
AU  - Cline JM
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Clarkson, Thomas B
AU  - Clarkson TB
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Carr, J Jeffrey
AU  - Carr JJ
AD  - 5 Department of Radiology Vanderbilt University School of Medicine Nashville TN.
FAU - Kitzman, Dalane W
AU  - Kitzman DW
AD  - 4 Section on Cardiology Department of Internal Medicine Wake Forest University 
      School of Medicine Winston-Salem NC.
FAU - Register, Thomas C
AU  - Register TC
AD  - 1 Section on Comparative Medicine Department of Pathology Wake Forest University 
      School of Medicine Winston-Salem NC.
LA  - eng
GR  - P30 AG021332/AG/NIA NIH HHS/United States
GR  - P30 AG049638/AG/NIA NIH HHS/United States
GR  - R01 AG018915/AG/NIA NIH HHS/United States
GR  - T32 OD010957/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 4TI98Z838E (Estradiol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*physiology
MH  - Diastole/*drug effects/*physiology
MH  - Estradiol/*pharmacology
MH  - Extracellular Matrix/*physiology
MH  - Female
MH  - Gene Expression/*drug effects
MH  - Heart/*drug effects
MH  - Homeostasis/*physiology
MH  - Macaca fascicularis
MH  - Myocardium
MH  - *Ovariectomy
MH  - Postoperative Period
MH  - Random Allocation
MH  - Time Factors
PMC - PMC6404177
OTO - NOTNLM
OT  - diastolic dysfunction
OT  - estrogen
OT  - fibrosis
OT  - menopause
OT  - transcriptome
EDAT- 2018/12/21 06:00
MHDA- 2019/12/18 06:00
PMCR- 2018/11/06
CRDT- 2018/12/21 06:00
PHST- 2018/12/21 06:00 [entrez]
PHST- 2018/12/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/11/06 00:00 [pmc-release]
AID - JAH33593 [pii]
AID - 10.1161/JAHA.118.009769 [doi]
PST - ppublish
SO  - J Am Heart Assoc. 2018 Nov 6;7(21):e009769. doi: 10.1161/JAHA.118.009769.