Author + information
- Received March 26, 2020
- Revision received June 22, 2020
- Accepted June 23, 2020
- Published online September 28, 2020.
- Jahn M. Firth, PhDa,
- Hsiang-Yu Yang, MD, PhDb,
- Alice J. Francis, BSca,
- Najah Islam, BSca and
- Kenneth T. MacLeod, PhDa,∗ ()
- aNational Heart and Lung Institute, Imperial College, Hammersmith Hospital, London, United Kingdom
- bCardiovascular Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (R.O.C.)
- ↵∗Address for correspondence:
Dr. Kenneth T. MacLeod, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
• During the progression toward heart failure, indicators of in vivo whole-heart function suggest greater impairment in the absence of estrogen.
• At the single cardiac myocyte level, the absence of estrogen results in further reduction of Ca2+ transient amplitudes, further slowing of transient decay kinetics, less SR Ca2+ content, and a further increase in Ca2+ spark frequencies and spark-mediated SR leak compared with animals with normal estrus cycles.
• Cardiac myocyte Na+ regulation is also more disrupted in the absence of estrogen.
Contradictory findings of estrogen supplementation in cardiac disease highlight the need to investigate the involvement of estrogen in the progression of heart failure in an animal model that lacks traditional comorbidities. Heart failure was induced by aortic constriction (AC) in female guinea pigs. Selected AC animals were ovariectomized (ACOV), and a group of these received 17β-estradiol supplementation (ACOV+E). One hundred-fifty days post-AC surgery, left-ventricular myocytes were isolated, and their electrophysiology and Ca2+ and Na+ regulation were examined. Long-term absence of ovarian hormones exacerbates the decline in cardiac function during the progression to heart failure. Estrogen supplementation reverses these aggravating effects.
This work was supported by the British Heart Foundation [Project Grant Number: PG/032/27241], London, United Kingdom, to Dr. MacLeod. Dr. Yang has received funding from Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (R.O.C.). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 26, 2020.
- Revision received June 22, 2020.
- Accepted June 23, 2020.
- 2020 The Authors