Abstract
The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent years, microRNAs have been established as non-coding RNAs that regulate the expression of a high percentage of protein-coding genes in mammals and are related to the correct function of human physiology. Moreover, within the cardiovascular system, miRNAs have been related to physiological and pathological conditions. In this review, we address what is known about the role of estrogen-regulated miRNAs and their emerging involvement in vascular biology.
Highlights
Estrogen is involved in many physiological processes, including sexual development and reproduction, regulation of skeletal homeostasis, lipid and carbohydrate metabolism, electrolyte balance, central nervous system function, and cardiovascular system regulation [1,2]
During the fifth decade of a woman’s life, the decrease in estrogen levels that occurs in menopause is accompanied by an increase in the incidence of cardiovascular diseases [6,7], suggesting that estrogen plays a beneficial role in cardiovascular system
DICER1 knockdown resulted in impaired proliferation and vessel formation, as well as altered expression of key proteins implicated in vascular tone regulation and angiogenesis, such as vascular endothelial growth factor receptor 2 (VEGFR), interleukin 8 (IL-8), and endothelial nitric oxide (NO) synthases [88,89], suggesting a role of miRNAs production in endothelial and vascular function
Summary
Estrogen is involved in many physiological processes, including sexual development and reproduction, regulation of skeletal homeostasis, lipid and carbohydrate metabolism, electrolyte balance, central nervous system function (including cognition and behavior), and cardiovascular system regulation [1,2]. The phenomenon, referred to as the “timing hypothesis”, postulates that the beneficial effects of hormonal replacement in the prevention of cardiovascular disease may occur only when hormonal supplementation is initiated before the detrimental effects that aging has on the cardiovascular system have become established [11] In this regard, it has been reported that age moderates the vasodilatory [12] and anti-inflammatory [13] effects that estrogen have on vascular tissue in postmenopausal women. Estrogen signaling is selectively regulated by the relative balance between ERα and ERβ expression in target organs [23], studies using ERα and ERβ knockout mice revealed that the beneficial effects estrogen has on the vascular system are mainly mediated by ERα [24,25] Besides their classic genomic action, ERs can trigger faster responses (in minutes) through plasma membrane receptors. Many of the beneficial effects of estrogen seen in human and animal models, such as reduced myocardial pro-inflammatory cytokine expression, inhibition of VSMC proliferation, and nitric oxide (NO)-dependent vasodilation [28], have been recently attributed to the presence of GPER in the cardiovascular system
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