ArticleThrombosis research2012
PDE4 regulates tissue plasminogen activator expression of human brain microvascular endothelial cells.
Article in Thrombosis research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Association between PDE4D rs966221 polymorphism and risk of ischemic stroke: a systematic review and meta-analysis.Metabolic brain disease · 2018Pooled it
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Article
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- Luteolin suppresses inflammation through inhibiting cAMP-phosphodiesterases activity and expression of adhesion molecules in microvascular endothelial cells.Inflammopharmacology · 2019Article
- Article
- Tissue Plasminogen Activator Causes Brain Microvascular Endothelial Cell Injury After Oxygen Glucose Deprivation by Inhibiting Sonic Hedgehog Signaling.Neurochemical research · 2019Article
- Effects of PDE4 pathway inhibition in rat experimental stroke.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties.Journal of the neurological sciences · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
introductionFactors regulating brain tissue plasminogen activator (tPA) are pertinent for stroke. Recent observations have suggested a role for the phosphodiesterase-4 (PDE4) pathway in stroke pathogenesis, via an uncertain mechanism. We studied PDE4 regulation of tPA expression by human brain microvascular endothelial cells in a variety of conditions, including an in vitro model of ischemia. MATERIALS AND
methodsWe analyzed tPA antigen and mRNA of human brain microvascular endothelial cells (HBECs) during normoxia and oxygen-glucose deprivation (OGD) following inhibition of PDE4 and PDE4D, using HBEC monocultures and co-cultures with astrocytes and pericytes, and analyzed relevant signal transduction pathways.
resultsPDE4 inhibitor rolipram enhanced OGD effects on endothelial tPA release in endothelial monocultures and co-cultures with astrocytes; there was a 54±10% (p<0.001) reduction of tPA release in astrocyte-endothelial co-cultures under OGD. PDE4D siRNA reduced endothelial tPA mRNA to 40-55% of control (p<0.05). Use of Epac inducer mimicked, while use of Epac siRNA inhibited, these effects.
conclusionsInhibition of PDE4 and PDE4D reduced expression of tPA by HBEC via Epac pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.