Sex differences in the vascular function and related mechanisms: role of 17β-estradiol

Pabbidi, Mallikarjuna R.; Kuppusamy, Maniselvan; Didion, Sean P.; Sanapureddy, Padmaja; J, Reed; Sontakke, Sumit P.

doi:10.1152/ajpheart.00194.2018

Cited by 69 publications

(55 citation statements)

References 274 publications

(363 reference statements)

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“…It is known that the estrogens differently influence the function of VSMCs and ECs, depending on sex, and the distribution and expression of estrogen receptors seem to be one of the most important factors. Estradiol increases the production of NO and PGI2 and inhibits the release of TXA2 and superoxide in the endothelium, while in VSMCs, it regulates the function of K + channels [29]. It is known that estrogens may modulate the activity of a vascular purinergic system, although there was no evidence of estrogen participation in the control of the extracellular nucleotide metabolism specifically in the aorta.…”

Section: Discussionmentioning

confidence: 99%

Effect of estradiol on enzymes of vascular extracellular nucleotide metabolism

2020

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Purpose Estrogens have beneficial effects on the cardiovascular system, promoting vasodilation, endothelial cells growth, relaxation, and regulation of blood pressure. Some of these effects could be associated with the purinergic system known for the control of vasodilation, inflammation, and platelet function. The aim of our study was the evaluation of ATP, AMP, and adenosine extracellular catabolism, catalyzed by ectonucleoside triphosphate diphosphohydrolase-1 (CD39), ecto-5′-nucleotidase (CD73), and ecto-adenosine deaminase (eADA) in mouse aortas. Methods Extracellular hydrolysis of ATP, AMP, and adenosine was estimated on the aortic surface of 3-month-old female and male C57BL/6 J wild-type (WT) mice, in female WT mouse aortas incubated for 48 h in the presence or absence of 100 nM estradiol, and in WT female mouse and ApoE-/-LDL-R-/- aortas. The conversion of substrates to products was analyzed by high-pressure liquid chromatography (HPLC). Results We demonstrated significantly higher adenosine deamination rate in WT male vs. female mice (p = 0.041). We also noted the lower adenosine hydrolysis in aortas exposed to estradiol, as compared with the samples incubated in estradiol-free medium (p = 0.043). Finally, we observed that adenosine conversion to inosine was significantly higher on the surface of ApoE-/-LDL-R-/- aortas compared with WT mice (p = 0.001). No such effects were noted in ATP and AMP extracellular hydrolysis. Conclusion We conclude that estradiol inhibits the extracellular degradation of adenosine to inosine, which may be an element of its vascular protective effect, as it will lead to an increase in extracellular adenosine concentration. We can also assume that during the development of the atherosclerotic process, the protective role of estradiol in the regulation of adenosine degradation may be obscured by other pathogenic factors.

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Section: Discussionmentioning

confidence: 99%

Effect of estradiol on enzymes of vascular extracellular nucleotide metabolism

2020

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“…Estrogens can also act through non-genomic actions mediated by membrane-bound ERα (mERα) and ERβ (mERβ), as well as the membrane-bound G-proteincoupled estrogen receptor GPER1 (also known as GPR30) [15][16][17]. Even though estrogens' effects on the NVU are the most well described [18], we will focus on androgens in this review and would like to refer the readers to Robison et al 2019 for more details on estrogen effects [19].…”

Section: Androgens' Modes Of Actionmentioning

confidence: 99%

Androgens’ effects on cerebrovascular function in health and disease

2020

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Androgens affect the cerebral vasculature and may contribute to sex differences in cerebrovascular diseases. Men are at a greater risk for stroke and vascular contributions to cognitive impairment and dementia (VCID) compared to women throughout much of the lifespan. The cerebral vasculature is a target for direct androgen actions, as it expresses several sex steroid receptors and metabolizing enzymes. Androgens' actions on the cerebral vasculature are complex, as they have been shown to have both protective and detrimental effects, depending on factors such as age, dose, and disease state. When administered chronically, androgens are shown to be pro-angiogenic, promote vasoconstriction, and influence blood-brain barrier permeability. In addition to these direct effects of androgens on the cerebral vasculature, androgens also influence other vascular risk factors that may contribute to sex differences in cerebrovascular diseases. In men, low androgen levels have been linked to metabolic and cardiovascular diseases including hypertension, diabetes, hyperlipidemia, and obesity, which greatly increase the risk of stroke and VCID. Thus, a better understanding of androgens' interactions with the cerebral vasculature under physiological and pathological conditions is of key importance.

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“…In general, women at ages before the beginning of menopause are less vulnerable than men to present cardiovascular diseases (Pabbidi et al, 2018). K Ca 1.1 channels are key elements in the modulation of the vascular smooth muscle tone.…”

Section: Cardiovascular Systemmentioning

confidence: 99%

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

2020

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Many ion channels are involved in tumor development, promoting cancer cell proliferation, migration, invasion, and survival. Accordingly, some of them have been suggested as tumor markers and novel targets for cancer therapy. Some sex steroid hormones (SSH), including estrogens and androgens, favor cancer progression. Meanwhile, other steroid hormones like vitamin D may have anticancer properties. SSH and vitamin D modulate the expression of a number of ion channels in cancer cells from hormone-sensitive tissues, including breast, ovary, prostate, and cervix. Moreover, rapid effects of SSH may be mediated by their direct action on membrane ion channels. Here, we reviewed the SSH and vitamin D regulation of ion channels involved in cancer, and analyzed the potential molecular pathways implicated. In addition, we described the potential clinical use of ion channels in cancer diagnosis and therapy, taking advantage of their regulation by SSH and vitamin D. Since SSH are considered risk factors for different types of cancer, and ion channels play important roles in tumor progression, the regulation of ion channels by SSH and vitamin D may represent a potential opportunity for early cancer diagnosis and therapeutic approaches in SSH and vitamin D sensitive tumors.

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Sex differences in the vascular function and related mechanisms: role of 17β-estradiol

Cited by 69 publications

References 274 publications

Effect of estradiol on enzymes of vascular extracellular nucleotide metabolism

Effect of estradiol on enzymes of vascular extracellular nucleotide metabolism

Androgens’ effects on cerebrovascular function in health and disease

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

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