Evidence map›Paper›PMID 29385021›Full record

ReviewJournal of cardiovascular development and disease2018

PDE4-Mediated cAMP Signalling.

Bracy A Fertig, George S Baillie

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of cardiovascular development and disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

  1. A systematic review of novel Phosphodiesterase-4 inhibitors in the treatment of psoriasis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Article
  14. Review
  15. Article
  16. Mechanisms and Recent Advances of Small-Molecule Therapeutics in Rosacea Treatment.Clinical, cosmetic and investigational dermatology · 2025
    Review
  17. PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024
    Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Bracy A FertigUniversity of Glasgow, Glasgow G12 8QQ, UK. b.fertig.1@research.gla.ac.uk.
George S BaillieUniversity of Glasgow, Glasgow G12 8QQ, UK. george.baillie@glasgow.ac.uk.
University of Glasgow · GB

Funding

British Heart Foundation PG/17/26/32881Medical Research Council MR/J007412/1
6 · The paper itself

Abstract

cAMP is the archetypal and ubiquitous second messenger utilised for the fine control of many cardiovascular cell signalling systems. The ability of cAMP to elicit cell surface receptor-specific responses relies on its compartmentalisation by cAMP hydrolysing enzymes known as phosphodiesterases. One family of these enzymes, PDE4, is particularly important in the cardiovascular system, where it has been extensively studied and shown to orchestrate complex, localised signalling that underpins many crucial functions of the heart. In the cardiac myocyte, cAMP activates PKA, which phosphorylates a small subset of mostly sarcoplasmic substrate proteins that drive β-adrenergic enhancement of cardiac function. The phosphorylation of these substrates, many of which are involved in cardiac excitation-contraction coupling, has been shown to be tightly regulated by highly localised pools of individual PDE4 isoforms. The spatial and temporal regulation of cardiac signalling is made possible by the formation of macromolecular "signalosomes", which often include a cAMP effector, such as PKA, its substrate, PDE4 and an anchoring protein such as an AKAP. Studies described in the present review highlight the importance of this relationship for individual cardiac PKA substrates and we provide an overview of how this signalling paradigm is coordinated to promote efficient adrenergic enhancement of cardiac function. The role of PDE4 also extends to the vascular endothelium, where it regulates vascular permeability and barrier function. In this distinct location, PDE4 interacts with adherens junctions to regulate their stability. These highly specific, non-redundant roles for PDE4 isoforms have far reaching therapeutic potential. PDE inhibitors in the clinic have been plagued with problems due to the active site-directed nature of the compounds which concomitantly attenuate PDE activity in all highly localised "signalosomes".

Indexed as

cardiac myocytephosphodiesterase 4vascular endothelium

Identifiers

PMID29385021
PMCPMC5872356
OpenAlexW2791132131

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.