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March 1, 2004Journal of Clinical InvestigationOpen Access

Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats

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Why the study?

Does phospholamban inhibition via rAAV-S16EPLN gene transfer improve cardiac function and prevent remodeling in rats with established post-myocardial infarction heart failure?

Population

34 adult male Sprague-Dawley rats with established heart failure 5 weeks after myocardial infarction

Comparison

S16EPLN delivered by transcoronary gene transfer… vs Saline injection delivered by the same…

Design

Preclinical, Animals with an infarct size between 30% and 40% were randomized…

Follow-up

6 months

Key result

In rats with established heart failure after myocardial infarction, rAAV-mediated gene transfer of S16EPLN significantly improved left ventricular ejection fraction (36.4% vs 25.8%) and suppressed ventricular dilation at 6 months compared to saline.

Authors

YIYoshitaka IwanagaMHMasahiko HoshijimaYGYusu Gu

Discussion

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Overview

May support phospholamban-targeted gene therapy development; leaves open translation from rodent models to clinical use.

Structured PICO

Does phospholamban inhibition via rAAV-S16EPLN gene transfer improve cardiac function and prevent remodeling in rats with established post-myocardial infarction heart failure?

P
Population
34 adult male rats with established heart failure and 30-40% infarct size 5 weeks post-myocardial infarction, followed for 6 months after gene transfer.
I
Intervention
S16EPLN (pseudophosphorylated form of phospholamban mutant) delivered by transcoronary gene transfer using a recombinant adeno-associated virus (rAAV) vector (1.9 × 10⁹ genome copies per gram body weight in 2.0 ml volume)
C
Comparator
Saline injection (2.0 ml) delivered by the same transcoronary gene transfer procedure
O
Outcome
Left ventricular size and function (LVEF, LVEDV) assessed by echocardiography at 2 and 6 months after gene transfersurrogate

Main Result

Absolute Event Rate: 36.4% vs 25.8%

p-value: p=<0.05

Phospholamban inhibition via rAAV-mediated S16EPLN gene transfer improves cardiac function and attenuates pathological remodeling in a rat model of established post-MI heart failure.

Limitations

  • Limited transcoronary transduction efficiency (estimated at 60% or less of the cell population).
  • Significant inflammatory immune response observed with the rAAV-LacZ marker gene in rats.
  • Findings are from an animal model and may not directly translate to human clinical outcomes.

Cite This Study

Iwanaga et al. (2004) studied Heart failure after myocardial infarction (n=34). rAAV-S16EPLN gene transfer vs. Saline injection was evaluated on Left ventricular ejection fraction (LVEF) at 6 months (p=<0.05). In rats with established heart failure after myocardial infarction, rAAV-mediated gene transfer of S16EPLN significantly improved left ventricular ejection fraction (36.4% vs 25.8%) and suppressed ventricular dilation at 6 months compared to saline.

synapsesocial.com/papers/6a730c0891c366bb2031e6ffhttps://doi.org/10.1172/jci200418716
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats2004 · 174 citations
  2. 2rAAV-asPLB Transfer Attenuates Abnormal Sarcoplasmic Reticulum Ca2+-ATPase Activity and Cardiac Dysfunction in Rats with Myocardial Infarction2007 · 13 citations
  3. 3AAV‐mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes2007 · 28 citations
  4. 4Antisense Therapy Attenuates Phospholamban p.(Arg14del) Cardiomyopathy in Mice and Reverses Protein Aggregation2022 · 25 citations
  5. 5Rescue of cardiomyocyte dysfunction by phospholamban ablation does not prevent ventricular failure in genetic hypertrophy2003 · 113 citations