Targeting PDE3/4 to allow regulation of cardiac calcium homeostasis in disease

Project Details


After myocardial infarction (MI), patients have reduced cardiac function and are more susceptible to arrhythmia. β-blockers
are the most common antiarrhythmic treatment, but the further reduction in cardiac contractility is problematic. This study
will investigate the benefit of targeting regulators of cellular calcium cycling, to increase contractility, but maintain the
antiarrhythmic effects of β-blockade. The inotropic effect of phospholamban (PLB) phosphorylation is well established and
is also antiarrhythmic. We have discovered that the only phosphodiseterase type 4 (PDE4) regulating PLB is PDE4D5.
We know that PDE’s target subcellular microdomains; distinct isoforms localise with all cardiac Ca2+ cycling targets. We
will explore the function of PDE4D5 attached to the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)/PLB complex.
We have recently uncovered the interaction sites between PDE4D5 and the SERCA complex and have started to develop
a peptide which prevents PDE4D5 binding near SERCA/PLB. These data may justify further work to develop and test a
drug which targets this PDE-SERCA interaction.
Effective start/end date1/04/2112/10/23


  • British Heart Foundation: £129,254.00

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being


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