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December 6, 2014AJP Heart and Circulatory PhysiologyOpen Access

Overexpression of adenylyl cyclase type 5 (AC5) confers a proarrhythmic substrate to the heart

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Key result

Cardiac-specific overexpression of adenylyl cyclase type 5 (AC5) prolonged action potential duration and increased susceptibility to isoproterenol-induced arrhythmias in mice.

Why the study?

Does overexpression of adenylyl cyclase type 5 (AC5) promote arrhythmogenesis in a transgenic mouse model?

Population

AC5 transgenic (AC5Tg) mice and wild-type (WT) mice (ventricular myocytes and in vivo models)

Comparison

Adenylyl cyclase type 5 overexpression, with or… vs Wild-type (WT) mice and myocytes

Design

Preclinical

Authors

ZZZhenghang ZhaoXi'an Jiaotong UniversityGBGopal J. BabuRutgers, The State University of New JerseyHWHairuo WenNational Medical Products Administration

Discussion

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Member takes

Overview

Highlights a potential mechanism for beta-adrenergic arrhythmias; leaves open whether targeting adenylyl.

Structured PICO

Does overexpression of adenylyl cyclase type 5 (AC5) promote arrhythmogenesis in a transgenic mouse model?

P
Population
AC5 transgenic (AC5Tg) mice and wild-type (WT) mice (ventricular myocytes and in vivo models)
I
Intervention
Adenylyl cyclase type 5 (AC5) overexpression, with or without isoproterenol treatment
C
Comparator
Wild-type (WT) mice and myocytes
O
Outcome
Arrhythmogenesis and underlying cellular mechanisms (SR Ca2+ content, fractional Ca2+ release, twitch Ca2+ transient, action potential duration, spontaneous Ca2+ waves, and afterdepolarizations)surrogate

Main Result

Absolute Event Rate: 65.2% vs 46.7%

p-value: p=<0.05

AC5 overexpression confers a proarrhythmic substrate in the heart by inducing SR calcium overload and RyR hyperactivation, highlighting a potential mechanism for beta-adrenergic mediated arrhythmias.

Limitations

  • Animal model findings may not directly translate to human clinical arrhythmias.
  • Further mechanistic studies are needed to assess the synergistic roles of differential signaling pathways in causing arrhythmias in AC5Tg hearts.

Cite This Study

Zhao et al. (2014) studied Arrhythmias. Adenylyl cyclase type 5 (AC5) overexpression vs. Wild-type (WT) was evaluated on Action potential duration at 90% repolarization (APD90) in ms (p=<0.05). Cardiac-specific overexpression of adenylyl cyclase type 5 (AC5) prolonged action potential duration and increased susceptibility to isoproterenol-induced arrhythmias in mice.

synapsesocial.com/papers/6a158b1ad64fa333899fcaadhttps://doi.org/10.1152/ajpheart.00630.2014
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Also Consider

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  1. 1Calmodulin Kinase II and Arrhythmias in a Mouse Model of Cardiac Hypertrophy2002 · 269 citations
  2. 2Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction2006 · 105 citations
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