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

Abstract

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 Ca2+ 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.

• Authors: Allan K Alencar, Jaqueline S da Silva, Marina Lin, Ananssa M Silva, Xuming Sun, Carlos M Ferrario, Cheping Cheng, Roberto T Sudo, Gisele Zapata-Sudo, Hao Wang, Leanne Groban
• Journal: The journals of gerontology. Series A, Biological sciences and medical sciences (J Gerontol A Biol Sci Med Sci) Vol. 72 Issue 2 Pg. 152-162 (02 2017) ISSN: 1758-535X [Electronic] United States
• PMID: 27006078 (Publication Type: Journal Article)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Estrogens
• Gper1 protein, rat
• Receptors, G-Protein-Coupled

Topics

• Age Factors
• Animals
• Estrogens (physiology)
• Female
• Heart (anatomy & histology, physiology)
• Rats
• Rats, Inbred BN
• Rats, Inbred F344
• Receptors, G-Protein-Coupled (physiology)