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Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

Morris, G, Puri, BK, Olive, Lisa, Carvalho, A, Berk, Michael, Walder, Ken, Gustad, LT and Maes, Michael 2020, Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments, BMC Med, vol. 18, no. 1, pp. 1-31, doi: 10.1186/s12916-020-01749-w.

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Title Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments
Author(s) Morris, G
Puri, BK
Olive, LisaORCID iD for Olive, Lisa orcid.org/0000-0003-4643-8561
Carvalho, A
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Walder, KenORCID iD for Walder, Ken orcid.org/0000-0002-6758-4763
Gustad, LT
Maes, Michael
Journal name BMC Med
Volume number 18
Issue number 1
Article ID 305
Start page 1
End page 31
Total pages 31
Publisher BMC
Place of publication London, Eng.
Publication date 2020-10-19
ISSN 1741-7015
1741-7015
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
NF-KAPPA-B
C-REACTIVE PROTEIN
NITRIC-OXIDE SYNTHASE
POLYUNSATURATED FATTY-ACIDS
MAJOR DEPRESSIVE DISORDER
SEROTONIN REUPTAKE INHIBITORS
LOW-DENSITY-LIPOPROTEIN
CORONARY-HEART-DISEASE
NECROSIS-FACTOR-ALPHA
KRUPPEL-LIKE FACTOR-2
Summary Background: Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. Main text: Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. Conclusions: Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.
Language eng
DOI 10.1186/s12916-020-01749-w
Indigenous content off
Field of Research 11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, The Authors
Free to Read? Yes
Use Rights Maes, M
Persistent URL http://hdl.handle.net/10536/DRO/DU:30144374

Document type: Journal Article
Collections: Faculty of Health
School of Psychology
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.