Hydrogen Sulfide Restored the Diurnal Variation in Cardiac Function of Aging Mice.

Huaxing Zhang,Xiangjian Zhang,Xu Teng,Sheng Jin,Yuming Wu,Danyang Tian,Jing Dai,Qi Guo,Hongmei Xue,Lin Xiao,Oluwakemi Josephine Awakan

doi:10.1155/2021/8841575

Huaxing Zhang, Xiangjian Zhang + Show 9 more

Open Access

https://doi.org/10.1155/2021/8841575

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Abstract

The present study was performed to investigate whether H2S could restore the diurnal variation in cardiac function of aging mice and explore the potential mechanisms. We found that ejection fraction (EF) and fractional shortening (FS) in 3-month-old mice exhibited diurnal variations over a 24-hour period. However, the diurnal variations were disrupted in 18-month-old mice, and there was a decline in EF and FS. In addition, the plasma malondialdehyde (MDA) levels were increased, and H2S concentrations and superoxide dismutase (SOD) activities were decreased in 18-month-old mice. Then, CSE KO mice were used to determine if there was a relationship between endogenous H2S and diurnal variations in EF and FS. There was no difference in 12-hour averaged EF and FS between dark and light periods in CSE KO mice accompanying increased MDA levels and decreased SOD activities in plasma, indicating that deficiency of endogenous H2S blunted diurnal variations of cardiac function. To determine whether oxidative stress disrupted the diurnal variations in cardiac function, D-galactose-induced subacute aging mice were employed. After 3-month D-gal treatment, both 12-hour averaged EF and FS in dark or light periods were decreased; meanwhile, there was no difference in 12-hour averaged EF and FS between dark and light periods. After 3-month NaHS treatment in the D-gal group, the plasma MDA levels were decreased and SOD activities were increased. The EF and FS were lower during the 12-hour light period than those during the 12-hour dark period which was fit to sine curves in the D-gal+NaHS group. Identical findings were also observed in 18-month-old mice. In conclusion, our studies revealed that the disrupted diurnal variation in cardiac function was associated with increased oxidative stress and decreased H2S levels in aging mice. H2S could restore the diurnal variation in cardiac function of aging mice by reducing oxidative stress.

Highlights

Because of the planet’s rotation, life on earth has evolved strategies to better adapt its physiology and behaviors to diurnal cycles of around 24 h
The 4-hour interval data showed that both ejection fraction (EF) and fractional shortening (FS) were significantly lower during the 12hour light period than those during the 12-hour dark period (Figures 1(b) and 1(d)), and the minimum and maximum values were observed at 16:00 and 4:00, respectively, which were fit to sine curves
Both EF and FS in 18-month-old mice were comparable between the 12-hour light period and the 12-hour dark period, indicating that diurnal variations in EF and FS were disrupted in aging mice

Summary

Introduction

Because of the planet’s rotation, life on earth has evolved strategies to better adapt its physiology and behaviors to diurnal cycles of around 24 h. The epidemiologic, clinical, and experimental studies demonstrate the profound importance of this 24 h circadian variation for healthy cardiovascular physiology, and disruption is associated with increased risk of heart disease and worsens outcome [3,4,5]. During various disease states (including aging), the circadian variation of cardiac function is often attenuated/abolished which is contributing to high morbidity and mortality of cardiovascular diseases in the elderly [6,7,8]. Several lines of evidence suggested that increasing oxidative stress was one of the main characteristics and drivers of aging and age-related disorders [9, 10]. It has been reported that there was a bidirectional relationship between oxidative stress and circadian rhythms as redox status could influence circadian clock function, while clock proteins

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