IMR Press / FBL / Volume 29 / Issue 1 / DOI: 10.31083/j.fbl2901046
Open Access Original Research
Early Estrogen Replacement Therapy Attenuates Cardiac Dysfunction Caused by Aging and Ovariectomy in Female Wistar Rats
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1 Laboratorio de Farmacología del Miocardio, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, 54740 Estado de México, Mexico
2 Laboratorio de Farmacología Molecular, Escuela Superior de Medicina, Instituto Politécnico Nacional, 11340 Ciudad de México, Mexico
3 Laboratorio de Patología, Instituto Nacional de Cardiología Dr. Ignacio Chávez. CDMX. Tlalpan, 14080 Ciudad de México, Mexico
*Correspondence: jfmqfb@gmail.com (Jazmin Flores-Monroy)
Front. Biosci. (Landmark Ed) 2024, 29(1), 46; https://doi.org/10.31083/j.fbl2901046
Submitted: 15 June 2023 | Revised: 31 August 2023 | Accepted: 8 October 2023 | Published: 24 January 2024
(This article belongs to the Special Issue Lipids and lipid metabolism in cardiovascular disease)
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Cardiovascular diseases (CVDs) are the leading cause of women’s mortality, linked to aging and reduced estrogen during menopause. Estrogen replacement therapy (ERT) is suggested for CVDs prevention. Yet, its timing initiation remains contentious. Thus, we aimed to evaluate the effect of early and late estrogen therapy on cardiac function and lipid metabolism in ovariectomized old female Wistar rats. Methods: Fifty randomized female Wistar rats were included in 5 groups (n = 10, 18 months old): (1) Sham, (2) 10 weeks post ovariectomy (Ovx-10 w), (3) 10 weeks post Ovx + early estrogen replacement therapy (Ovx 10 w-early ERT), (4) 20 weeks post Ovx (Ovx-20 w) and (5) Ovx 20 w-late ERT. Three days (early ERT) or 10 weeks (late ERT) after surgery 17-β estradiol was given (5 µg/kg/day), and 10 weeks after the start of ERT, we assessed cardiac function by echocardiography, electrocardiography, and cardiac catheterization. Estradiol, cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were determined. Cardiac histology was performed with Masson’s staining. Results: Ovariectomy (Ovx) increases left ventricle internal systolic diameter (0.4 vs 0.3 cm, *p = 0.020) and decreases shortening fraction (40 vs 54 %, *p = 0.030) regardless of therapy. ERT prevents the increase in left ventricle mass after 10 weeks post-Ovx and the ejection fractionreduction after 20 weeks. Lower P wave amplitudes (18.8 vs 24.2 ms, *p = 0.013) were found in the Ovx-20 w group. A longer duration of the QRS complex after 20 weeks post-Ovx with and without ERT was found (32.5 and 32.1 vs 28.3 ms, *p = 0.003; *p = 0.007). Diastolic blood pressure was higher 20 weeks post-Ovx (86 vs 76 mmHg, *p = 0.047), regardless of ERT. The left ventricle (LV) –dP/dt was decreased in Ovx groups without ERT (–750 vs –1320 mmHg, *p = 0.034). An increase in LV collagen deposition was found in the Ovx 10 w group vs Sham (9.58 vs 4.54 %, *p = 0.028). Early ERT avoids the increase in body weight, cholesterol and LDL caused by Ovx. Conclusions: Ovariectomy causes time-dependent alterations in lipid metabolism, morphology, electrical activity, and heart contractile function. Early but not late ERT prevents some of these effects.

Keywords
estrogen-replacement-therapy
ovariectomy
aging
echocardiography
electrocardiography
fibrosis
lipid-metabolism
Funding
IN202022/UNAM-PAPIIT
IN217122I/UNAM-PAPIIT
CI2211/FES Cuautitlán
CI2259/FES Cuautitlán
A1-S-8958/CONACYT
Figures
Fig. 1.
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