Inflammation-induced endothelial to mesenchymal transition promotes brain endothelial cell dysfunction and occurs during multiple sclerosis pathophysiology

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.

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Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability

Diabetes Obesity and Metabolism ◽

10.1111/j.1463-1326.2008.00987.x ◽

2009 ◽

Vol 11 (5) ◽

pp. 480-490 ◽

Cited By ~ 66

Author(s):

C. L. Allen ◽

U. Bayraktutan

Keyword(s):

Endothelial Cell ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Endothelial Cell Dysfunction ◽

Brain Endothelial Cell ◽

Cell Dysfunction ◽

Blood Brain

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B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1601350113 ◽

2016 ◽

Vol 113 (41) ◽

pp. E6182-E6191 ◽

Cited By ~ 11

Author(s):

Luisa Klotz ◽

Ivan Kuzmanov ◽

Stephanie Hucke ◽

Catharina C. Gross ◽

Vilmos Posevitz ◽

...

Keyword(s):

T Cells ◽

Endothelial Cell ◽

T Cell ◽

Endothelial Cell Dysfunction ◽

Brain Endothelial Cell ◽

Lesion Formation ◽

Genetic Ablation ◽

Cell Dysfunction ◽

Regulatory Molecule ◽

Cns Autoimmunity

Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the blood–brain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice). Genetic ablation of a single immune-regulatory molecule in this model [i.e., B7-homolog 1 (B7-H1, PD-L1)] not only significantly increased incidence of spontaneous CNS autoimmunity and aggravated disease course, especially in the later stages of disease, but also importantly resulted in encephalitogenic T-cell infiltration and lesion formation in normally unaffected brain regions, such as the cerebrum and cerebellum. Interestingly, B7-H1 ablation on myelin oligodendrocyte glycoprotein-specific CD4+ T cells, but not on antigen-presenting cells, amplified T-cell effector functions, such as IFN-γ and granzyme B production. Therefore, these T cells were rendered more capable of eliciting cell contact-dependent brain endothelial cell dysfunction and increased barrier permeability in an in vitro model of the BBB. Our findings suggest that a single immune-regulatory molecule on T cells can be ultimately responsible for localized BBB breakdown, and thus substantial changes in lesion topography in the context of CNS autoimmunity.

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Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

Nutrients ◽

10.3390/nu13072282 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2282

Author(s):

Valentina Masola ◽

Mario Bonomini ◽

Maurizio Onisto ◽

Pietro Manuel Ferraro ◽

Arduino Arduini ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Viability ◽

Biological Effects ◽

Membrane Integrity ◽

Glucose Content ◽

Mesenchymal Transition ◽

Low Glucose ◽

Endothelial To Mesenchymal Transition ◽

Osmotic Agents

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

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Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Journal of Endocrinology ◽

10.1530/joe-16-0340 ◽

2017 ◽

Vol 232 (1) ◽

pp. R27-R44 ◽

Cited By ~ 90

Author(s):

D S Boeldt ◽

I M Bird

Keyword(s):

Endothelial Cell ◽

Endothelial Dysfunction ◽

Cell Function ◽

Endothelial Cell Dysfunction ◽

Hypertensive Disorders Of Pregnancy ◽

Endothelial Cell Function ◽

Vascular Adaptation ◽

Cell Dysfunction ◽

Maternal Adaptation ◽

Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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