title: 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.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Allan K
authors.initials: AK
authors.lastname: Alencar
authors.affiliation: Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Marina
authors.initials: M
authors.lastname: Lin
authors.affiliation: Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ananssa M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Xuming
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.affiliation: Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Cheping
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sudo
authors.affiliation: Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina. lgroban@wakehealth.edu.|Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.|The Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina.|The Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000367:Age Factors; D000818:Animals; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006321:Heart / Q000033:anatomy & histology* / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D004967:Estrogens; C520305:Gper1 protein, rat; D043562:Receptors, G-Protein-Coupled
keywords: Diastolic dysfunction; Fibrosis; Menopause; Ovariectomy; Phospholamban; SERCA2