Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat

Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricu...

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Veröffentlicht in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2017-02, Vol.72 (2), p.152-162
Hauptverfasser: Alencar, Allan K, da Silva, Jaqueline S, Lin, Marina, Silva, Ananssa M, Sun, Xuming, Ferrario, Carlos M, Cheng, Cheping, Sudo, Roberto T, Zapata-Sudo, Gisele, Wang, Hao, Groban, Leanne
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container_title The journals of gerontology. Series A, Biological sciences and medical sciences
container_volume 72
creator Alencar, Allan K
da Silva, Jaqueline S
Lin, Marina
Silva, Ananssa M
Sun, Xuming
Ferrario, Carlos M
Cheng, Cheping
Sudo, Roberto T
Zapata-Sudo, Gisele
Wang, Hao
Groban, Leanne
description Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricular diastolic dysfunction, echocardiograms were performed in 10 middle-aged (20 months) and 30 old-aged (30 months) female Fischer344×Brown-Norway rats, 4 and 8 weeks after ovariectomy (OVX) and sham procedures (gonads left intact). The cardioprotective potential of administering chronic G1, the selective agonist to the new G-protein-coupled estrogen receptor (GPER), was further evaluated in old rats (Old-OVX+G1) versus age-matched, vehicle-treated OVX and gonadal intact rats. Advanced age and estrogen loss led to decreases in myocardial relaxation and elevations in filling pressure, in part, due to reductions in phosphorylated phospholamban and increases in cardiac collagen deposition. Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca ATPase expression and reductions in interstitial fibrosis. These findings may explain the preponderance of heart failure with preserved ejection fraction in older postmenopausal women and provide a promising, late-life therapeutic target to reverse or halt the progression of left ventricular diastolic dysfunction.
doi_str_mv 10.1093/gerona/glw045
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Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca ATPase expression and reductions in interstitial fibrosis. 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source MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection
subjects Age Factors
Animals
Estrogens - physiology
Female
Heart - anatomy & histology
Heart - physiology
Original
Rats
Rats, Inbred BN
Rats, Inbred F344
Receptors, G-Protein-Coupled - physiology
title Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat
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