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May 9, 2000CirculationOpen Access

Adenovirus-Based Phospholamban Antisense Expression as a Novel Approach to Improve Cardiac Contractile Dysfunction

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Why the study?

Does adenovirus-based phospholamban antisense expression improve Ca(2+) handling in cultured rat neonatal cardiomyocytes?

Population

Cultured rat neonatal cardiomyocytes

Comparison

Adenovectors expressing phospholamban antisense… vs Adenovectors expressing PL sense RNA or baseline

Design

Preclinical

Follow-up

up to 72 hours

Key result

Infection of cultured rat neonatal cardiomyocytes with Ad5CMVPLas reduced PL mRNA to 30% and PL protein to 24% of baseline, increasing Ca2+ sensitivity of SERCA2.

Authors

KEKarin EizemaHFHenry FechnerKBKarel Bezstarosti

Discussion

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Overview

May improve diastolic function via PL antisense; leaves open clinical translation in human HF.

Structured PICO

Does adenovirus-based phospholamban antisense expression improve Ca(2+) handling in cultured rat neonatal cardiomyocytes?

P
Population
Cultured rat neonatal cardiomyocytes.
I
Intervention
Adenovectors expressing phospholamban (PL) antisense RNA under the control of a constitutive cytomegalovirus (CMV) promoter (Ad5CMVPLas) or an inducible atrial natriuretic factor (ANF) promoter (Ad5ANFPLas)
C
Comparator
Adenovectors expressing PL sense RNA (Ad5CMVPLs or Ad5ANFPLs) or baseline
O
Outcome
Reduction in PL mRNA and protein levels, Ca(2+) sensitivity of SERCA2, and time to 50% recovery of the Ca(2+) transientsurrogate

Adenovirus-mediated phospholamban antisense RNA expression successfully downregulates phospholamban and improves calcium handling in cardiomyocytes, suggesting a potential gene therapy approach for heart failure.

Cite This Study

Eizema et al. (2000) studied Cardiac contractile dysfunction. Adenovirus-based phospholamban (PL) antisense RNA (Ad5CMVPLas and Ad5ANFPLas) vs. Adenovectors expressing PL sense RNA (Ad5CMVPLs and Ad5ANFPLs) was evaluated on PL mRNA and protein levels. Infection of cultured rat neonatal cardiomyocytes with Ad5CMVPLas reduced PL mRNA to 30% and PL protein to 24% of baseline, increasing Ca2+ sensitivity of SERCA2.

synapsesocial.com/papers/6a5dee7e488486c5eff67911https://doi.org/10.1161/01.cir.101.18.2193
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Also Consider

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

  1. 1Targeting Phospholamban by Gene Transfer in Human Heart Failure2002 · 277 citations
  2. 2Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes1997 · 124 citations
  3. 3AAV‐mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes2007 · 28 citations
  4. 4Rescue of Ca<sup>2+</sup> overload-induced left ventriclur dysfunction by targeted ablation of phospholamban2008 · 44 citations
  5. 5Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus1999 · 41 citations