Estrogen-mediated mitigation of cardiac oxidative stress in ovariectomized rats is associated with upregulated cardiac circadian clock Per2 and heart-specific miRNAs

Aug 24, 2023Life sciences

Estrogen may reduce heart oxidative stress in rats without ovaries by increasing heart clock gene Per2 and heart-specific microRNAs

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Abstract

OVX + E2 rats exhibited lower mean arterial pressure (MAP) during both day and night times.

Higher levels of the circadian clock protein Per2 and cardioprotective microRNAs were found in the hearts of OVX + E2 rats.
Lower levels of reactive oxygen species and cardio-detrimental microRNA652 were observed in the same group.
A correlation was noted between the upregulated cardioprotective microRNAs and the relationship between Per2 and HO-1 during daytime.
Cardiac levels of Per2, heart-specific microRNAs, and redox enzyme activities were similar between normal female and OVX + E2 rats.

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AIM: Estrogen (E2) confers cardioprotection in premenopausal women and in models of menopause and its effects, mostly studied in female reproductive organs, vary on a circadian rhythm basis in relation to the circadian clock genes. However, it remains unknown if a similar circadian pattern exists in the female heart in a manner that explains, at least partly, the cardioprotective effect of E2. The aim of the present investigation was to determine if upregulation of the circadian clock Per2 and its regulated heart-specific miRNAs, and redox enzymes contribute to the E2-mediated cardioprotection in ovariectomized rats.

MAIN METHODS: Rats were subjected to ovariectomy (OVX) 2-weeks prior to a 2-week E2 treatment. On the last treatment day, hearts were collected every 4 h. for ex-vivo biochemical measurements. In parallel studies, telemetric mean arterial pressure (MAP) was obtained at the tissue collection times.

KEY FINDINGS: OVX + E2 rats exhibited lower body weight during daytime and MAP during day and night times, and their hearts exhibited: (1) higher Per2 protein abundance, cardioprotective miRNAs (miRNA1, miRNA133a, miRNA208a, miRNA499), mALDH2, and catalase; (2) lower reactive oxygen species, cardio-detrimental miRNA652, carbonyl, MDA and HO-1 levels. The reciprocal Per2/HO-1 relationship was more evident during the daytime and correlated with the upregulated cardioprotective miRNAs in OVX + E2 rats. Finally, cardiac Per2, heart-specific miRNAs and reactive oxygen species levels and redox enzymes activities were similar in normal female and OVX + E2 rats.

SIGNIFICANCE: Enhancement of cardiac Per2, redox enzymes and heart-specific miRNAs likely contribute to E2-mediated mitigation of cardiac oxidative stress in OVX rats.

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Estrogen-mediated mitigation of cardiac oxidative stress in ovariectomized rats is associated with upregulated cardiac circadian clock Per2 and heart-specific miRNAs

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