scholarly journals Response to Letter to the editor from Behar-Cohen, et al: The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

2021 ◽  
Author(s):  
Joost Brinks ◽  
Elon H C van Dijk ◽  
Robbert G E Notenboom ◽  
Paul H A Quax ◽  
Camiel J F Boon ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Central Serous Chorioretinopathy ◽  
Cortisol Response ◽  
Male And Female ◽  
Letter To The Editor

scholarly journals The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

2021 ◽  
Author(s):  
Joost Brinks ◽  
Elon H C van Dijk ◽  
Szymon M Kiełbasa ◽  
Hailiang Mei ◽  
Isa van der Veen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sex Differences ◽  
Glucocorticoid Receptor ◽  
Central Serous Chorioretinopathy ◽  
Target Genes ◽  
Transcriptional Response ◽  
Cortisol Response ◽  
Vascular Integrity ◽  
Interindividual Differences ◽  
Vascular Regulation

Abstract Context Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80-90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown. Design and Objective We aimed to reveal the potential steroidal contribution to CSC. We characterized the expression of the glucocorticoid-, mineralocorticoid-, and androgen receptor in the human choroid, using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors. Results The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid- and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences, but very few sex differences. Several highly regulated genes such as ZBTB16 (log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation. Conclusions The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions.

Gestational diabetes alters microRNA signatures in human feto-placental endothelial cells depending on fetal sex

2018 ◽  
Vol 132 (22) ◽  
pp. 2437-2449 ◽  
Author(s):  
Jasmin Strutz ◽  
Silvija Cvitic ◽  
Hubert Hackl ◽  
Karl Kashofer ◽  
Hannah M. Appel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Gestational Diabetes ◽  
Endothelial Function ◽  
Mirna Expression ◽  
Maternal Body Mass Index ◽  
Separate Analysis ◽  
Biological Functions ◽  
Metabolic Disturbances ◽  
Fetal Sex ◽  
Male And Female

MicroRNAs (miRNAs), small non-coding RNAs, have emerged as important, epigenetic regulators of endothelial function. Metabolic disturbances such as diabetes alter miRNA expression. In adults, the miRNA transcriptome as well as endothelial function differ between the sexes. Here, we hypothesized that metabolic disturbances associated with gestational diabetes (GDM) alter miRNA signatures in feto-placental endothelial cells (fpEC), dependent on fetal sex. We isolated human primary fpEC after normal and GDM-complicated pregnancies with male and female neonates and screened for differential miRNA expression using next-generation miRNA sequencing. To test for miRNAs commonly regulated in fpEC of female and male progeny, data were stratified for fetal sex and maternal body mass index (BMI). Analyses were also performed separately for female and male fpEC, again accounting for maternal BMI as covariate. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath software. Maternal GDM altered 26 miRNA signatures when male and female fpEC were analyzed together. Separate analysis of male versus female fpEC revealed 22 GDM affected miRNAs in the females and only 4 in the males, without overlap. Biological functions potentially modulated by the affected miRNAs related to ‘Protein Processing in Endoplasmic Reticulum’ and ‘Proteoglycans in Cancer’. Maternal GDM alters miRNA signatures in fpEC, and biological functions affected by these miRNAs relate to well-known adverse functional consequences of diabetes on endothelium. GDM effects were highly dependent on fetal sex with miRNA signatures in female fpEC being more susceptible to metabolic derangements of GDM than miRNAs in male fpEC.

Gender and transcriptional regulation of NO synthase and ET-1 in porcine aortic endothelial cells

1997 ◽  
Vol 273 (4) ◽  
pp. H1962-H1967 ◽  
Author(s):  
Xiaofang Wang ◽  
Dustan A. Barber ◽  
Debra A. Lewis ◽  
Christopher G. A. McGregor ◽  
Gary C. Sieck ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Western Blot ◽  
Northern Blot ◽  
Blot Analysis ◽  
Northern Blot Analysis ◽  
Ovarian Hormones ◽  
Intact Male ◽  
Male And Female ◽  
Aortic Endothelial Cells

Experiments were designed to determine whether normal fluctuations in sex steroid hormones alter gene transcription for endothelial nitric oxide synthase (NOS) and preproendothelin-1 (prepro-ET-1). Aortic endothelial cells were removed from adult, gonadally intact male and female or ovariectomized Yorkshire pigs. Endothelial cells were prepared for Northern blot analysis, Western blot analysis or enzyme activity. Nitric oxide products (NOx) and endothelin-1 (ET-1) in plasma were measured by chemiluminescence and radioimmunoassay, respectively. Northern blot analysis identified single bands corresponding to endothelial NOS and prepro-ET-1. Quantification of the blots showed an increase in expression of mRNA for both endothelial NOS and prepro-ET-1 in ovariectomized pigs compared with gonadally intact male and female pigs. There were no differences in amount of endothelial NOS protein identified by Western blot analysis among groups. On the contrary, plasma concentrations of NOx were significantly decreased in ovariectomized pigs, and there were no differences either in the concentrations of ET-1 in the plasma or extracts from the coronary arteries. These results suggest that expression of endothelial NOS and prepro-ET-1 may be regulated at transcriptional level by ovarian hormones. In addition, the ovarian hormones may regulate production of these endothelium-derived factors at the posttranscriptional level.

scholarly journals Sex-dependent differences in the secretome of human endothelial cells

2020 ◽  
Author(s):  
Maria Grazia Cattaneo ◽  
Cristina Banfi ◽  
Maura Brioschi ◽  
Donatella Lattuada ◽  
Lucia M. Vicentini
Keyword(s):  
Endothelial Cells ◽  
Secreted Proteins ◽  
Mrna Levels ◽  
Preclinical Research ◽  
Male And Female ◽  
Human Male ◽  
Pharmacological Targets ◽  
Endothelial Response ◽  
Significant Enrichment ◽  
Male Specific

Abstract Background: Cellular sex has been rarely considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and ‘omics approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.Methods: We performed proteomic and gene ontology (GO) analyses of secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and western blot techniques, and efferocytosis through the ability of the macrophage cell line RAW-264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR. Results: Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison to female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggests that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seems to be independent on PTX3 expression. Conclusions: Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.

scholarly journals Sex-Dependent Differences in the Secretome of Human Endothelial Cells

2020 ◽  
Author(s):  
Maria Grazia Cattaneo ◽  
Cristina Banfi ◽  
Maura Brioschi ◽  
Donatella Lattuada ◽  
Lucia M. Vicentini
Keyword(s):  
Endothelial Cells ◽  
Secreted Proteins ◽  
Human Endothelial Cells ◽  
Preclinical Research ◽  
Male And Female ◽  
Human Male ◽  
Pharmacological Targets ◽  
Endothelial Response ◽  
Significant Enrichment ◽  
Male Specific

Abstract Background: Cellular sex has been rarely considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and ‘omics approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.Methods: We performed proteomic and gene ontology (GO) analyses of secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and western blot techniques, and efferocytosis through the ability of the macrophage cell line RAW-264.7 to engulf apoptotic ECs. Protein expression and silencing efficacy were assessed by RT-qPCR. Results: Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison to female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 proved that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis was independent of PTX3 expression. Conclusions: Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.

scholarly journals Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Roberta Addis ◽  
Ilaria Campesi ◽  
Marco Fois ◽  
Giampiero Capobianco ◽  
Salvatore Dessole ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Male And Female

scholarly journals An Investigation of Hair Cortisol Concentration across Body Sites and within Hair shaft

2010 ◽  
Vol 3 ◽  
pp. CMED.S4465 ◽  
Author(s):  
Christopher F. Sharpley ◽  
Kathleen G. Kauter ◽  
James R. Mcfarlane
Keyword(s):  
Young Male ◽  
Hair Shaft ◽  
Cortisol Concentration ◽  
Cortisol Response ◽  
Hair Cortisol ◽  
Shaft Length ◽  
Male And Female ◽  
Environmental Demand

Cortisol concentrations in hair collected from young male and female adults were assayed and compared for differences along shaft length and between body sites. No significant differences were found between hair shaft sites, supporting a model of the hair shaft as “alive” and responsive to environmental demand in terms of cortisol production. Hair taken from forearms had significantly higher concentrations of cortisol than hair from lower legs, suggesting a localized hair cortisol response and verifying previous findings. Issues of the link between central and peripheral HPA axes are raised for discussion and further investigation.

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