Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Sex Hormones and Cardiovascular Pathophysiology: New Insights into Mechanism(s) of...
share announcement

Sex Hormones and Cardiovascular Pathophysiology: New Insights into Mechanism(s) of Action and Therapeutic Use

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Cardiovascular System".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 8537

Special Issue Editor

Prof. Dr. Raghvendra Dubey

E-Mail Website
Guest Editor
Department for Reproductive Endocrinology, University Zurich, CH8952 Schlieren, Switzerland
Interests: sex hormones and cardiovascular pathophysiology: mechanism(s) of action and therapeutic insights
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues:

Gender differences in cardiovascular disease highlight the potential role of sex steroids in actively regulating the cardiovascular system. The last two decades have seen in-depth research on the mechanism(s) via which female and male sex hormones, estrogen(s) and androgen(s), can influence cardiovascular function. More importantly, new therapeutic strategies for safer and effective use of hormone therapy, particularly estrogen replacement, have been outlined following the WHI and HERs trials. Since cardiovascular disease involves multiple cells (endothelial cells, smooth muscle cells, macrophages, monocytes, progenitor cells, etc.), processes (growth, inflammation, cell death, calcification) and mechanisms (estrogen receptors and estrogen metabolism), it is important to revisit the recent developments and highlight the future directions in this regard. The importance of sex hormones in regulating cardiovascular function may also be linked to COVID-associated cardiovascular complications in males and females.

Prof. Dr. Raghvendra Dubey
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

23 pages, 5934 KiB  
Article
Estradiol Inhibits Human Brain Vascular Pericyte Migration Activity: A Functional and Transcriptomic Analysis
by Lisa Kurmann, Michal Okoniewski and Raghvendra K. Dubey
Cells 2021, 10(9), 2314; https://doi.org/10.3390/cells10092314 - 4 Sep 2021
Cited by 6 | Viewed by 3106
Abstract
Stroke is the third leading cause of mortality in women and it kills twice as many women as breast cancer. A key role in the pathophysiology of stroke plays the disruption of the blood–brain barrier (BBB) within the neurovascular unit. While estrogen induces [...] Read more.
Stroke is the third leading cause of mortality in women and it kills twice as many women as breast cancer. A key role in the pathophysiology of stroke plays the disruption of the blood–brain barrier (BBB) within the neurovascular unit. While estrogen induces vascular protective actions, its influence on stroke remains unclear. Moreover, experiments assessing its impact on endothelial cells to induce barrier integrity are non-conclusive. Since pericytes play an active role in regulating BBB integrity and function, we hypothesize that estradiol may influence BBB by regulating their activity. In this study using human brain vascular pericytes (HBVPs) we investigated the impact of estradiol on key pericyte functions known to influence BBB integrity. HBVPs expressed estrogen receptors (ER-α, ER-β and GPER) and treatment with estradiol (10 nM) inhibited basal cell migration but not proliferation. Since pericyte migration is a hallmark for BBB disruption following injury, infection and inflammation, we investigated the effects of estradiol on TNFα-induced PC migration. Importantly, estradiol prevented TNFα-induced pericyte migration and this effect was mimicked by PPT (ER-α agonist) and DPN (ER-β agonist), but not by G1 (GPR30 agonist). The modulatory effects of estradiol were abrogated by MPP and PHTPP, selective ER-α and ER-β antagonists, respectively, confirming the role of ER-α and ER-β in mediating the anti-migratory actions of estrogen. To delineate the intracellular mechanisms mediating the inhibitory actions of estradiol on PC migration, we investigated the role of AKT and MAPK activation. While estradiol consistently reduced the TNFα-induced MAPK and Akt phosphorylation, only the inhibition of MAPK, but not Akt, significantly abrogated the migratory actions of TNFα. In transendothelial electrical resistance measurements, estradiol induced barrier function (TEER) in human brain microvascular endothelial cells co-cultured with pericytes, but not in HBMECs cultured alone. Importantly, transcriptomics analysis of genes modulated by estradiol in pericytes showed downregulation of genes known to increase cell migration and upregulation of genes known to inhibit cell migration. Taken together, our findings provide the first evidence that estradiol modulates pericyte activity and thereby improves endothelial integrity. Full article
(This article belongs to the Special Issue Sex Hormones and Cardiovascular Pathophysiology: New Insights into Mechanism(s) of Action and Therapeutic Use)
►▼ Show Figures

Figure 1

23 pages, 6011 KiB  
Article
Proteomic Analysis of Estrogen-Mediated Enhancement of Mesenchymal Stem Cell-Induced Angiogenesis In Vivo
by Maria Cristina Mihai, Mirel Adrian Popa, Viorel Iulian Șuică, Felicia Antohe, Edwin K. Jackson, Brigitte Leeners, Maya Simionescu and Raghvendra K. Dubey
Cells 2021, 10(9), 2181; https://doi.org/10.3390/cells10092181 - 24 Aug 2021
Cited by 4 | Viewed by 2746
Abstract
Therapeutic use of mesenchymal stem cells (MSCs) for tissue repair has great potential. MSCs from multiple sources, including those derived from human umbilical matrix, namely Wharton’s jelly, may serve as a resource for obtaining MSCs. However, low in vivo engraftment efficacy of MSCs [...] Read more.
Therapeutic use of mesenchymal stem cells (MSCs) for tissue repair has great potential. MSCs from multiple sources, including those derived from human umbilical matrix, namely Wharton’s jelly, may serve as a resource for obtaining MSCs. However, low in vivo engraftment efficacy of MSCs remains a challenging limitation. To improve clinical outcomes using MSCs, an in-depth understanding of the mechanisms and factors involved in successful engraftment is required. We recently demonstrated that 17β-estradiol (E2) improves MSCs in vitro proliferation, directed migration and engraftment in murine heart slices. Here, using a proteomics approach, we investigated the angiogenic potential of MSCs in vivo and the modulatory actions of E2 on mechanisms involved in tissue repair. Specifically, using a Matrigel® plug assay, we evaluated the effects of E2 on MSCs-induced angiogenesis in ovariectomized (OVX) mice. Moreover, using proteomics we investigated the potential pro-repair processes, pathways, and co-mechanisms possibly modified by the treatment of MSCs with E2. Using RT-qPCR, we evaluated mRNA expression of pro-angiogenic molecules, including endoglin, Tie-2, ANG, and VEGF. Hemoglobin levels, a marker for blood vessel formation, were increased in plugs treated with E2 + MSCs, suggesting increased capillary formation. This conclusion was confirmed by the histological analysis of capillary numbers in the Matrigel® plugs treated with E2 + MSC. The LC-MS screening of proteins obtained from the excised Matrigel® plugs revealed 71 proteins that were significantly altered following E2 exposure, 57 up-regulated proteins and 14 down-regulated proteins. A major result was the association of over 100 microRNA molecules (miRNAs) involved in cellular communication, vesicle transport, and metabolic and energy processes, and the high percentage of approximately 25% of genes involved in unknown biological processes. Together, these data provide evidence for increased angiogenesis by MSCs treated with the sex hormone E2. In conclusion, E2 treatment may increase the engraftment and repair potential of MSCs into tissue, and may promote MSC-induced angiogenesis after tissue injury. Full article
(This article belongs to the Special Issue Sex Hormones and Cardiovascular Pathophysiology: New Insights into Mechanism(s) of Action and Therapeutic Use)
►▼ Show Figures

Graphical abstract

17 pages, 5316 KiB  
Article
17β-Estradiol-Induced Conformational Changes of Human Microsomal Triglyceride Transfer Protein: A Computational Molecular Modelling Study
by Yong-Xiao Yang, Peng Li, Pan Wang and Bao-Ting Zhu
Cells 2021, 10(7), 1566; https://doi.org/10.3390/cells10071566 - 22 Jun 2021
Cited by 1 | Viewed by 2053
Abstract
Human microsomal triglyceride transfer protein (hMTP) plays an essential role in the assembly of apoB-containing lipoproteins, and has become an important drug target for the treatment of several disease states, such as abetalipoproteinemia, fat malabsorption and familial hypercholesterolemia. hMTP is a heterodimer composed [...] Read more.
Human microsomal triglyceride transfer protein (hMTP) plays an essential role in the assembly of apoB-containing lipoproteins, and has become an important drug target for the treatment of several disease states, such as abetalipoproteinemia, fat malabsorption and familial hypercholesterolemia. hMTP is a heterodimer composed of a larger hMTPα subunit and a smaller hMTPβ subunit (namely, protein disulfide isomerase, hPDI). hPDI can interact with 17β-estradiol (E2), an endogenous female sex hormone. It has been reported that E2 can significantly reduce the blood levels of low-density lipoprotein, cholesterol and triglyceride, and modulate liver lipid metabolism in vivo. However, some of the estrogen’s actions on lipid metabolism are not associated with estrogen receptors (ER), and the exact mechanism underlying estrogen’s ER-independent lipid-modulating action is still not clear at present. In this study, the potential influence of E2 on the stability of the hMTP complex is investigated by jointly using multiple molecular dynamics analyses based on available experimental structures. The molecular dynamics analyses indicate that the hMTP complex in the presence of E2 has reduced interface contacts and surface areas. A steered molecular dynamics analysis shows that the forces required to separate the two subunits (namely, hPDI and hMTPα subunit) of the hMTP complex in the absence of E2 are significantly higher than the forces required to separate the complex in which its hPDI is already bound with E2. E2 makes the interface between hMTPα and hPDI subunits more flexible and less stable. The results of this study suggest that E2-induced conformational changes of the hMTP complex might be a novel mechanism partly accounting for the ER-independent lipid-modulating effect of E2. Full article
(This article belongs to the Special Issue Sex Hormones and Cardiovascular Pathophysiology: New Insights into Mechanism(s) of Action and Therapeutic Use)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop