MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez, Xavier; Pérez‐Cremades, Daniel; Mompeón, Ana; Dantas, Ana Paula; Novella, Susana; Hermenegildo, Carlos

doi:10.1159/000487910

Cited by 43 publications

(33 citation statements)

References 56 publications

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“…Estrogen used in this study was 17β ‐ estradiol (Sigma) and the concentration was 1 nmol/L which is the physiological concentration in premenopausal women; the treatment time is 24 hours. To study the effects of estrogen, control groups without estrogen and estrogen‐added groups were designed.…”

Section: Methodsmentioning

confidence: 99%

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

et al. 2019

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Problem: Osteoarthritis (OA) is a chronic disease with a very high incidence and the pathology of which is quite complex. Epidemiological investigation showed that OA may be related to smoking and estrogen levels, but there are few studies focused on the cross-effect of these two factors. This research aims to investigate the molecular mechanism of nicotine and estrogen effects on chondrocytes to study the effect of smoking on the incidence of osteoarthritis in women. Method of the study:Nicotine was added to obtain inflammatory supernatants of macrophages, which were used to induce chondrocyte inflammation. Toluidine staining and immunohistochemistry were used to detect the extracellular matrix (ECM) of chondrocytes, while the important proteins in the metabolism of chondrocytes were detected by Western blot. Results: Nicotine-induced inflammatory supernatant promoted the degradation of ECM, such as type II collagen, aggrecan and proteoglycan 4. While in the presence of physiological concentrations of estrogen, this destructive effect is reversed. On the molecular level, estrogen (17β-estradiol, 1 nmol/L) can inhibit the matrix degrading enzymes and promote the transforming growth factor (TGF)-β1 pathway which is involved in matrix synthesis. However, in the presence of inflammatory induction, although estrogen could still inhibit the expression of matrix degrading enzymes, it inhibited the TGF-β1 pathway. Moreover, the different inflammatory factors in the inflammatory supernatant, mainly tumor necrosis factor-α, interleukin-1β, had different effects on the metabolic processes of chondrocytes. Conclusion: Estrogen reverses nicotine-induced inflammation mainly via reducing the degradation of ECM. The cross-effect of estrogen and inflammatory factor inhibitors can be a potential clinical reference for OA patients. K E Y W O R D S chondrocytes, estrogen, extracellular matrix, nicotine, osteoarthritis | INTRODUC TI ONOsteoarthritis (OA) is one of the most common chronic, degenerative joint inflammations which can worldwide cause severe disabilities. 1 The pathology of this disease is very complex. Previous studies have found that estrogen is an important influencing factor that can inhibit the development of OA. 2 Recent studies also show that smoking has a certain impact on the occurrence of OA, but the specific mechanism is controversial. 3

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Section: Methodsmentioning

confidence: 99%

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

et al. 2019

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“…) and endothelial cells (Vidal‐Gomez et al . ). We recently demonstrated the involvement of different ERs in the expression of oestradiol‐regulated miRNAs by using specific ER agonists and antagonists.…”

Section: Oestrogen Receptors In the Cardiovascular Systemmentioning

confidence: 97%

“…Although most of the analysed miRNA were regulated by ERα, ERβ and GPER were also found to be involved in oestradiol‐regulated miRNA expression (Vidal‐Gomez et al . ). In addition, oestradiol can regulate miRNA expression by acting directly on its biosynthesis machinery (Gupta et al .…”

Section: Oestrogen Receptors In the Cardiovascular Systemmentioning

confidence: 97%

Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women

Novella

Pérez‐Cremades

Mompeón

et al. 2019

The Journal of Physiology

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Women show a lower incidence of cardiovascular diseases than age‐matched men, but this benefit disappears after menopause. Oestrogen‐mediated vascular actions are mainly attributed to oestradiol and exerted by oestrogen receptors (ERα, ERβ and G protein‐coupled oestrogen receptor), through rapid and/or genomic mechanisms, but these effects depend on ageing and inflammation. A cardiovascular approach in women's health has arisen due to controversy regarding oestrogen's beneficial impact as reported in experimental and observational studies and large randomized trials. These can be explained, in part, by two mutually non‐exclusive hypotheses. On the one hand, the timing hypothesis, which states that oestrogen‐mediated benefits occur before the detrimental effects of ageing are established in the vasculature; on the other hand, ageing and/or hormonal‐associated changes in ER expression that could lead to a deleterious imbalance in favour of ERβ over ERα, generally associated with higher inflammation and endothelial dysfunction. In experimental studies, oestradiol acting on ERα promotes the release of vasoactive compounds such as nitric oxide (NO) and prostacyclin, and shifts the angiotensin axis towards angiotensin 1–7 production. Mechanisms underlying oestradiol vascular function also include anti‐inflammatory and epigenetic modifications. 17β‐Oestradiol changes the transcriptomic profile of endothelial cells, and the involvement of miRNA in the regulatory pathways of vascular function reinforces assumptions regarding the vascular actions of oestrogen. Thus, the present Symposium Review aims to postulate the role of ERα in oestrogen modulation of endothelium‐derived mediators and vascular physiology, as well as its relationship with miRNA and inflammation, and elucidate how physiological changes in postmenopausal women counteract the observed effects.

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“…Recently, changes in the miRNA expression profile upon exposure of human umbilical vein endothelial cells (HUVECs) to oestradiol revealed oestradiol‐dependent regulation of vascular function via miRNA. miR‐378 h and miR‐1244 were down‐regulated, while miR‐30b‐5p, miR‐487a‐5p, miR‐4710 and miR‐501‐3p were over‐expressed after oestradiol treatment, and bioinformatic analysis revealed that these miRNAs and their mRNA targets are involved in regulatory networks in endothelial homeostasis such as in production of NO and ROS in macrophages, ET‐1 signalling, phospholipase C signalling, protein kinase A, Rho GTPases signalling and lipid metabolism (Pérez‐Cremades, Mompeón & Vidal‐Gómez, ; Vidal‐Gomez et al ., ). One of the direct targets of oestradiol is miR‐126‐3p.…”

Section: Oestradiol‐dependent Microrna Regulation Of Gene Expression mentioning

confidence: 97%

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

et al. 2019

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The steroid hormone, oestradiol, has pleiotropic functions. The protective effects of oestradiol are attributed to its anti-inflammatory, antioxidant, anti-atherogenic, anti-apoptotic, vasodilatory activities and regulation of micro RNA. Oestradiol upregulates endothelial nitric oxide synthase gene expression and increases the production of nitric oxide, an important vasodilator. It suppresses the renin-angiotensin system and monitors haemodynamic stress. The hormone maintains the integrity of blood vessels by reducing oxidative stress while upregulating the expression of antioxidant enzymes and prevents vascular inflammation by regulating pro-and anti-inflammatory cytokines. Aneurysmal subarachnoid haemorrhage (aSAH) occurring as a consequence of the rupture of an intracranial aneurysm is a devastating cerebrovascular event, representing 5-7% of all strokes. Postmenopausal women are more susceptible to aSAH compared to men in the same age group. This gender disparity has been attributed to reduced levels of the vascular protective hormone oestradiol following menopause. This review is focused on the protective role of oestradiol on vasculature and how the drop in oestradiol levels after menopause dramatically increases the incidence of aSAH in women. During menopause, oestradiol deficiency may affect vascular integrity causing dysregulation of vascular homeostasis by affecting the renin-angiotensin-aldosterone system (RAAS) and inflammatory and apoptotic cascades, resulting in the weakening of the cerebral arterial wall and potentially to development of an aneurysm and its rupture. In view of the role of oestradiol in maintaining vascular integrity, treatments involving hormone replacement could be a promising approach in postmenopausal women who are at risk of developing or rupturing an intracranial aneurysm.

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MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Cited by 43 publications

References 56 publications

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

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