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November 20, 2012Circulation ResearchOpen Access

Phosphodiesterase Type 3A Regulates Basal Myocardial Contractility Through Interacting With Sarcoplasmic Reticulum Calcium ATPase Type 2a Signaling Complexes in Mouse Heart

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Key result

PDE3A, but not PDE3B, is the primary isozyme modulating basal myocardial contractility and sarcoplasmic reticulum calcium content in mouse hearts.

Population

PDE3A(-/-) and PDE3B(-/-) mice and wild-type littermates (isolated hearts and cardiomyocytes)

Comparison

Genetic knockout of PDE3A or PDE3B, and… vs Wild-type littermates

Design

Preclinical

Authors

SBSanja BecaSuez Canal UniversityFAFaiyaz AhmadBudge Budge Institute of TechnologyWSWeixing ShenNanjing University of Chinese Medicine

Discussion

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Implication

PDE3A-selective targeting may enhance contractility; leaves open translation beyond murine models.

Structured PICO

P
Population
PDE3A(-/-) and PDE3B(-/-) mice and wild-type littermates (isolated hearts and cardiomyocytes)
E
Exposure
Genetic knockout of PDE3A or PDE3B, and pharmacological PDE3 inhibition
C
Comparator
Wild-type littermates
O
Outcome
Cardiac contractility and relaxation, Ca2+ transient amplitudes, and sarcoplasmic reticulum (SR) Ca2+ contentsurrogate

PDE3A, rather than PDE3B, is the primary isozyme modulating basal myocardial contractility and SR calcium content through interaction with the SERCA2a-phospholamban complex.

Cite This Study

Beca et al. (2012) studied this question. PDE3A knockout vs. Wild-type littermates and PDE3B knockout was evaluated on Cardiac contractility and relaxation. PDE3A, but not PDE3B, is the primary isozyme modulating basal myocardial contractility and sarcoplasmic reticulum calcium content in mouse hearts.

synapsesocial.com/papers/6a6d481be36a167817dff4d7https://doi.org/10.1161/circresaha.111.300003
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Mouse isolated perfused heart: Characteristics and cautions2003 · 94 citations
  2. 2Regulation of Phosphodiesterase 3 and Inducible cAMP Early Repressor in the Heart2007 · 116 citations
  3. 3Cardiac Sarcoplasmic Reticulum Calcium Release and Load Are Enhanced by Subcellular cAMP Elevations in PI3Kγ-Deficient Mice2005 · 31 citations
  4. 4Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice2006 · 183 citations