Postmenopausal health interventions: Time to move on from the Women’s Health Initiative?

Zaw, Jay Jay Thaung; Howe, Peter; Wong, Rachel H. X.

doi:10.1016/j.arr.2018.10.005

Cited by 51 publications

(38 citation statements)

References 73 publications

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“…No studies to-date have linked the NLRP3 inflammasome to the loss of estrogenic cardioprotection or inactivation of any one of the estrogen receptors. In the present study, using the cardiomyocyte-specific GPER knockout (KO) mouse, RT 2 Profiler TM real-time PCR array, and in vivo NLRP3 inhibition by its specific inhibitor, MCC950, we show, for the first time, that the NLRP3-related inflammatory pathway is involved in cardiac dysfunction related to GPER deficiency in cardiomyocytes.…”

Section: Introductionmentioning

confidence: 75%

“…Numerous preclinical studies demonstrate that estrogen protects the heart through both direct effects on cardiomyocytes, and indirectly via systemic effects [1]. However, hormone therapy over the past few decades has not shown clear cardiac benefits and might be associated with health risks including cancer, coronary heart disease, and stroke [2]. Furthering research on the mechanisms of estrogen in the attenuation of cardiovascular diseases, with a focus on roles of specific estrogen receptors, is critical in the development of more specific strategies for the treatment of cardiovascular diseases in women, with fewer or no side effects.…”

Section: Introductionmentioning

confidence: 99%

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NLRP3 inhibition improves heart function in GPER knockout mice

Wang

Sun

Hodge

et al. 2019

Biochemical and Biophysical Research Communications

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The molecular mechanisms of postmenopausal heart diseases in women may involve the loss of estrogen-deactivation of its membrane receptor, G-protein coupled estrogen receptor (GPER), and subsequent activation of the cardiac NLRP3 inflammasome, a component of the innate immune system. To study the potential effects of cardiac GPER on NLRP3-mediated inflammatory pathways, we characterized changes in innate immunity gene transcripts in hearts from 6-monthold cardiomyocyte-specific GPER knockout (KO) mice and their GPER-intact wild type (WT) littermates using RT 2 Profiler TM real-time PCR array. GPER deletion in cardiomyocytes decreased %fractional shortening (%FS) and myocardial relaxation (e΄), and increased the early mitral inflow filling velocity-to-early mitral annular descent velocity ratio (E/e΄), determined by echocardiography, and increased the mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), determined by real-time PCR. Of the 84 inflammasome-related genes tested, 9 genes were upregulated, including NLRP3 and IL-18, while 1 gene, IL-12a, was downregulated in GPER KO when compared to WT. The importance of NLRP3 upregulation in *

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

NLRP3 inhibition improves heart function in GPER knockout mice

Wang

Sun

Hodge

et al. 2019

Biochemical and Biophysical Research Communications

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“…Menopause and aging are two critical factors that are directly related to OP onset (Cheishvili et al, 2018). Postmenopausal osteoporosis (PMOP) is a major global public health concern that frequently presents in postmenopausal women due to estrogen deficiency and the continuous calcium loss that occurs with aging (Thaung Zaw, Howe & Wong, 2018). Osteoporotic fracture (OF) caused by OP is a major hazard and is one of the main causes of disability and death in older adults (Qaseem et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density

Huang

Wang

et al. 2020

PeerJ

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Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women are more susceptible to experiencing fragility fractures. Our study investigated the associations between circulating proteins with bone mineral density (BMD) in postmenopausal women with or without low BMD (osteoporosis and osteopenia) using a tandem mass tag (TMT) labeling proteomic experiment and parallel reaction monitoring testing. Across all plasma samples, we quantitatively measured 1,092 proteins, and the OP and normal control (NC) samples were differentiated by principal component analysis and a partial least squares-discrimination analysis model based on the protein profiling data. The differentially abundant proteins between the low BMD and NC samples mostly exhibited binding, molecular function regulator, transporter and molecular transducer activity, and were involved in metabolic and cellular processes, stimulus response, biological regulation, immune system processes and so forth. TMT analysis and RRM validation indicated that the expression of protein Lysozyme C (P61626) was negatively related to BMD, while the expression of proteins Glucosidase (A0A024R592) and Protein disulfideisomerase A5 (Q14554) was positively related to BMD values. Collectively, our results suggest that postmenopausal women with low BMD have a different proteomic profile or signature. Protein alterations may play an important role in the pathogenesis of PMOP, and they may act as novel biomarkers and targets of therapeutic agents for this disease.

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“…The latter is characterized by a permanent drop in estradiol and progesterone levels, and the consequent loss of the menstrual cycle and menstrual bleeding [10]. The decline in estradiol has several effects on women's physiology, resulting in increased risk of illness and poor quality of life [11]. Curiously, premenopausal and postmenopausal women are commonly at opposite ends of iron homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Menopause Delays the Typical Recovery of Pre-Exercise Hepcidin Levels after High-Intensity Interval Running Exercise in Endurance-Trained Women

et al. 2020

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Menopause commonly presents the gradual accumulation of iron in the body over the years, which is a risk factor for diseases such as cancer, osteoporosis, or cardiovascular diseases. Running exercise is known to acutely increase hepcidin levels, which reduces iron absorption and recycling. As this fact has not been studied in postmenopausal women, this study investigated the hepcidin response to running exercise in this population. Thirteen endurance-trained postmenopausal women (age: 51.5 ± 3.89 years; height: 161.8 ± 4.9 cm; body mass: 55.9 ± 3.6 kg; body fat: 24.7 ± 4.2%; peak oxygen consumption: 42.4 ± 4.0 mL·min−1·kg−1) performed a high-intensity interval running protocol, which consisted of 8 × 3 min bouts at 85% of the maximal aerobic speed with 90-second recovery. Blood samples were collected pre-exercise, 0, 3, and 24 hours post-exercise. As expected, hepcidin exhibited higher values at 3 hours post-exercise (3.69 ± 3.38 nmol/L), but also at 24 hours post-exercise (3.25 ± 3.61 nmol/L), in comparison with pre-exercise (1.77 ± 1.74 nmol/L; p = 0.023 and p = 0.020, respectively) and 0 hour post-exercise (2.05 ± 2.00 nmol/L; p = 0.021 and p = 0.032, respectively) concentrations. These differences were preceded by a significant increment of interleukin-6 at 0 hour post-exercise (3.41 ± 1.60 pg/mL) compared to pre-exercise (1.65 ± 0.48 pg/m, p = 0.003), 3 hours (1.50 ± 0.00 pg/mL, p = 0.002) and 24 hours post-exercise (1.52 ± 0.07 pg/mL, p = 0.001). Hepcidin peaked at 3 hours post-exercise as the literature described for premenopausal women but does not seem to be fully recovered to pre-exercise levels within 24 hours post-exercise, as it would be expected. This suggests a slower recovery of basal hepcidin levels in postmenopausal women, suggesting interesting applications in order to modify iron homeostasis as appropriate, such as the prevention of iron accumulation or proper timing of iron supplementation.

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Postmenopausal health interventions: Time to move on from the Women’s Health Initiative?

Cited by 51 publications

References 73 publications

NLRP3 inhibition improves heart function in GPER knockout mice

NLRP3 inhibition improves heart function in GPER knockout mice

Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density

Menopause Delays the Typical Recovery of Pre-Exercise Hepcidin Levels after High-Intensity Interval Running Exercise in Endurance-Trained Women

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