Estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor

Campesi, Ilaria; Capobianco, Giampiero; Dessole, Salvatore; Occhioni, Stefano; Montella, Andrea; Franconi, Flavia

doi:10.1159/000443403

Cited by 12 publications

(5 citation statements)

References 33 publications

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“…Bisphenol A (BPA) is produced in great quantities globally, primarily for use in polycarbonate plastics and epoxy resins, with the safety of human exposures to BPA being subject of intensive scientific assessment and regulatory efforts [59,168,169]. Since endocrine disruptors have implicated in a number of health concerns, including embryonic and early life development [164,170], progenitor cell function [171], female and male reproduction and development [164,172], infertility, cancer [172], autoimmune diseases [164], obesity and metabolic disorders [173,174] , epigenetic programming in adolescents [164,175], arterial hypertension [176], polycystic ovary syndrome (PCOS) [177][178][179] as well as deleterious effects of prenatal exposure to xenoestrogens [164,180]. Given that many endocrine disruptors also activate GPER future clinical research should be directed to explore which of the known estrogen receptors mediates their deleterious effects, and/or whether other mechanisms also play a role.…”

Section: Endocrine Disruptors and Xenoestrogens As Activators Of Gpermentioning

confidence: 99%

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER

Barton

2016

Steroids

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It has been 20years that the G protein-coupled estrogen receptor (GPER) was cloned as the orphan receptor GPR30 from multiple cellular sources, including vascular endothelial cells. Here, I will provide an overview of estrogen biology and the historical background leading to the discovery of rapid vascular estrogen signaling. I will also review the recent advances in the understanding of the mechanisms underlying GPER function, its role in physiology and disease, some of the currently available GPER-targeting drugs approved for clinical use such as SERMs (selective estrogen receptor modulators) and SERDs (selective estrogen receptor downregulators). Many of currently used drugs such as tamoxifen, raloxifene, or faslodex™/fulvestrant were discovered targeting GPER many years after they had been introduced to the clinics for entirely different purposes. This has important implications for the clinical use of these drugs and their modes of action, which I have termed 'reverse translational medicine'. In addition, environmental pollutants known as 'endocrine disruptors' have been found to bind to GPER. This article also discusses recent evidence in these areas as well as opportunities in translational clinical medicine and GPER research, including medical genetics, personalized medicine, prevention, and its theranostic use.

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Section: Endocrine Disruptors and Xenoestrogens As Activators Of Gpermentioning

confidence: 99%

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER

Barton

2016

Steroids

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“…Actually, botanicals are largely used [23,24], especially by women [25,26], but rigorous findings regarding their efficacy and safety profiles are still lacking [27]. Besides, the influence of sex on botanicals including EVOO, VOO, OO, and MPCs is also lacking; nevertheless, the individual's sex and gender is one of the most important modulators of CV health [28][29][30][31][32][33][34][35][36][37][38][39] and the numerous sex and gender differences at CV level are summarized in Table 1. Previously, we reviewed the sex-gender effect on polyphenols of various origins [25,26]; here we focus on EVOO and its MPCs because, as already mentioned, EFSA declares their utility in ameliorating low-density lipoproteins (LDL) oxidation and their importance in MedDiet [22].…”

Section: Introductionmentioning

confidence: 99%

Is Extra Virgin Olive Oil an Ally for Women’s and Men’s Cardiovascular Health?

Franconi

Campesi

Romani

2020

Cardiovascular Therapeutics

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Noncommunicable diseases are long-lasting and slowly progressive and are the leading causes of death and disability. They include cardiovascular diseases (CVD) and diabetes mellitus (DM) that are rising worldwide, with CVD being the leading cause of death in developed countries. Thus, there is a need to find new preventive and therapeutic approaches. Polyphenols seem to have cardioprotective properties; among them, polyphenols and/or minor polar compounds of extra virgin olive oil (EVOO) are attracting special interest. In consideration of numerous sex differences present in CVD and DM, in this narrative review, we applied “gender glasses.” Globally, it emerges that olive oil and its derivatives exert some anti-inflammatory and antioxidant effects, modulate glucose metabolism, and ameliorate endothelial dysfunction. However, as in prescription drugs, also in this case there is an important gender bias because the majority of the preclinical studies are performed on male animals, and the sex of donors of cells is not often known; thus a sex/gender bias characterizes preclinical research. There are numerous clinical studies that seem to suggest the benefits of EVOO and its derivatives in CVD; however, these studies have numerous limitations, presenting also a considerable heterogeneity across the interventions. Among limitations, one of the most relevant in the era of personalized medicine, is the non-attention versus women that are few and, also when they are enrolled, sex analysis is lacking. Therefore, in our opinion, it is time to perform more long, extensive and lessheterogeneous trials enrolling both women and men.

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“…It is already established that estrogens influence the function of the cells of the cardiovascular system, including platelets, leukocytes, vascular muscle, and endothelial cells. They induce vasodilation, induce the migration of endothelial cells, and decrease the inflammatory response and platelet aggregation [20,21]. There is some evidence of the possible involvement of estrogens in the regulation of purine extracellular metabolism.…”

Section: Introductionmentioning

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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Estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor

Cited by 12 publications

References 33 publications

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER

Is Extra Virgin Olive Oil an Ally for Women’s and Men’s Cardiovascular Health?

Effect of estradiol on enzymes of vascular extracellular nucleotide metabolism

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