Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Cyclic nucleotide phosphodiesterases (PDEs) and endothelial function in ischaemic stroke. A review

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. A switch-variant model integrates the functions of an autoimmune variant of the phosphatase PTPN22

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke: A systematic review of preclinical studies

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Time trends in incidence, comorbidity, and mortality of ischemic stroke in Denmark, 1996-2016

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Atypisk aura forårsaget af blodprop hos en 42-årig mand med migræne med aura.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. How to identify fatigue in stroke patients: an investigation of the post-stroke fatigue case definition validity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Første tilfælde af Mycobacterium chimaerainfektion relateret til åben thoraxkirurgi i Danmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND: Endothelial dysfunction is a hallmark of cerebrovascular disease, including ischemic stroke. Modulating endothelial signalling by cyclic nucleotides, cAMP and cGMP, is a potential therapeutic target in stroke. Inhibitors of the cyclic nucleotide degrading phosphodiesterase (PDE) enzymes may restore cerebral endothelial function. Current knowledge on PDE distribution and function in cerebral endothelial cells is sparse. This review explores data on PDE distribution and effects of PDEi in cerebral endothelial cells and identifies which PDEs are potential treatment targets in stroke.

METHOD: We performed a systematic search of electronic databases (Medline and Embase). Our search terms were cerebral ischaemia, cerebral endothelial cells, cyclic nucleotide, phosphodiesterase and phosphodiesterase inhibitors.

RESULTS: We found 23 publications which described effects of selective inhibitors of only three PDE families on endothelial function in ischemic stroke. PDE3 inhibitors (PDE3i) (11 publications) and PDE4 inhibitors (PDE4i) (3 publications) showed anti-inflammatory, anti-apoptotic or pro-angiogenic effects. PDE3i also reduced leucocyte infiltration and MMP-9 expression. Both PDE3i and PDE4i increased expression of tight junction proteins and protected the blood-brain barrier. PDE5 inhibitors (PDE5i) (6 publications) reduced inflammation and apoptosis. In preclinical models, PDE5i enhanced cGMP/NO signalling associated with microvascular angiogenesis, increased cerebral blood flow and improved functional recovery. Non-specific PDEi (3 publications) had mainly anti-inflammatory effects.

CONCLUSION: This review demonstrates that non-selective and selective PDEi of PDE3, PDE4 and PDE5 modulated endothelial function in cerebral ischemic stroke by regulating processes involved in vascular repair and neuroprotection and thus reduced cell death and inflammation. Of note, they promoted angiogenesis, microcirculation and improved functional recovery; all are important in stroke prevention and recovery, and effects should be further evaluated in humans.

OriginalsprogEngelsk
TidsskriftCellular Signalling
Vol/bind61
Sider (fra-til)108-119
Antal sider12
ISSN0898-6568
DOI
StatusUdgivet - sep. 2019

Bibliografisk note

Copyright © 2019. Published by Elsevier Inc.

ID: 59115857