About this Research Topic
Physiological deterioration and a greater susceptibility to disease are hallmarks of aging, which is an irreversible biological process. Despite aging affecting all species, sex differences exist. Women produce significant levels of estrogen during their reproductive years, mostly in the form of estradiol, which is believed to be particularly important for cardioprotection. Premenopausal women have a lower risk of cardiovascular disease than men, while postmenopausal women have a risk that matches or exceeds men's, implying that aging puts women at greater risk. Little is known about heart disease in women because they are underrepresented in studies and have fewer events than men like sudden cardiac arrest.
Over the last few decades, evidence from basic and preclinical investigations has shown that estrogens are cardioprotective, neuroprotective and improve cognitive function. Estrogens enhance synaptic plasticity, cholinergic neurotransmission, adult neurogenesis, and mitochondrial bioenergy. Nonetheless, extensive prospective clinical trials such as the Heart and Estrogen-Progestin Replacement Study and the Women's Health Initiative (WHI) failed to demonstrate a reduction in cardiac events among postmenopausal women receiving hormone replacement therapy. The unanticipated poor outcomes of postmenopausal estrogen replacement experiments are most likely due to our lack of understanding of the hormone's various effects.
Premenopausal women exhibit more pronounced vagal and moderate sympathetic activity than age-matched men, and this is mediated via estrogen. Sympathetic activity is gender-specific, and post-menopausal women have the greatest population burden of heart disease, including sudden cardiac arrest and heart failure, because estrogen levels have plateaued and hormonal impacts on vagal tone have changed. Furthermore, estrogen imparts cardioprotection by decreasing oxidative stress, increasing respiration and ATP production rates, and increasing the expression and/or activity of metabolic enzymes within mitochondria. Loss of estrogen alters mitochondrial membrane fatty acids, making them more susceptible to peroxidation, a characteristic also seen in organ-dependent aging. Estrogen imparts neuroprotection in a cholinergic-dependent way by regulating cognitive function. Studies show that estrogen normalizes frontal and occipital brain activation and reduces anticholinergic-induced verbal memory deficits, creating a “young adult” phenotype, thereby normalizing the effects of aging. However, similar to the effect of estrogen replacement on cardiovascular disease, its purported preventive effects may be limited to early postmenopausal women only, supporting the "critical window hypothesis." This adds a new degree of complexity to the study of how sex hormones influence things like mood, cardiovascular illness, fine motor skills, and neuroprotection in the brain.
Complex and understudied, the underlying mechanisms, benefits, and limitations of using this hormone to prevent cardiovascular disease warrant further exploration. This Research Topic intends to concentrate on the mechanism of estrogen signaling, with a particular emphasis on those systems that may play a significant role in cardioprotective.
We welcome submissions (reviews, original research, opinions) that cover (but are not limited to) the following areas:
•Menopause, Estrogen Signaling and Cardiovascular Disease in Women
•Estrogen signaling, mitochondria function, and oxidative stress
•Estrogen signaling and autonomic nervous system
•Sympathetic nervous system, vagal withdrawal, and heart disease in menopausal transition
•All molecular pathways that change during menopause
•Depression, menopause transition, and cardiovascular disease risk
•Hormone replacement therapy and cardiovascular health/ cognitive health
Over the last few decades, evidence from basic and preclinical investigations has shown that estrogens are cardioprotective, neuroprotective and improve cognitive function. Estrogens enhance synaptic plasticity, cholinergic neurotransmission, adult neurogenesis, and mitochondrial bioenergy. Nonetheless, extensive prospective clinical trials such as the Heart and Estrogen-Progestin Replacement Study and the Women's Health Initiative (WHI) failed to demonstrate a reduction in cardiac events among postmenopausal women receiving hormone replacement therapy. The unanticipated poor outcomes of postmenopausal estrogen replacement experiments are most likely due to our lack of understanding of the hormone's various effects.
Premenopausal women exhibit more pronounced vagal and moderate sympathetic activity than age-matched men, and this is mediated via estrogen. Sympathetic activity is gender-specific, and post-menopausal women have the greatest population burden of heart disease, including sudden cardiac arrest and heart failure, because estrogen levels have plateaued and hormonal impacts on vagal tone have changed. Furthermore, estrogen imparts cardioprotection by decreasing oxidative stress, increasing respiration and ATP production rates, and increasing the expression and/or activity of metabolic enzymes within mitochondria. Loss of estrogen alters mitochondrial membrane fatty acids, making them more susceptible to peroxidation, a characteristic also seen in organ-dependent aging. Estrogen imparts neuroprotection in a cholinergic-dependent way by regulating cognitive function. Studies show that estrogen normalizes frontal and occipital brain activation and reduces anticholinergic-induced verbal memory deficits, creating a “young adult” phenotype, thereby normalizing the effects of aging. However, similar to the effect of estrogen replacement on cardiovascular disease, its purported preventive effects may be limited to early postmenopausal women only, supporting the "critical window hypothesis." This adds a new degree of complexity to the study of how sex hormones influence things like mood, cardiovascular illness, fine motor skills, and neuroprotection in the brain.
Complex and understudied, the underlying mechanisms, benefits, and limitations of using this hormone to prevent cardiovascular disease warrant further exploration. This Research Topic intends to concentrate on the mechanism of estrogen signaling, with a particular emphasis on those systems that may play a significant role in cardioprotective.
We welcome submissions (reviews, original research, opinions) that cover (but are not limited to) the following areas:
•Menopause, Estrogen Signaling and Cardiovascular Disease in Women
•Estrogen signaling, mitochondria function, and oxidative stress
•Estrogen signaling and autonomic nervous system
•Sympathetic nervous system, vagal withdrawal, and heart disease in menopausal transition
•All molecular pathways that change during menopause
•Depression, menopause transition, and cardiovascular disease risk
•Hormone replacement therapy and cardiovascular health/ cognitive health
Keywords: Postmenopausal Women, Cardiovascular Disease, Oxidative Stress, Autonomic Nervous System, Estrogen, Hormone Replacement Therapy
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