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Cited by 66Cardiac electrophysiology and arrhythmiasCardiovascular Function and Risk FactorsCardiomyopathy and Myosin Studies

Parvalbumin gene transfer corrects diastolic dysfunction in diseased cardiac myocytes

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Wahr, Philip A., Michele, Daniel E., Metzger, Joseph M.·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.21.11982PMC PMC18398
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Abstract

Heart failure frequently involves diastolic dysfunction that is characterized by a prolonged relaxation. This prolonged relaxation is typically the result of a decreased rate of intracellular Ca 2+ sequestration. No effective treatment for this decreased Ca 2+ sequestration rate currently exists. As an approach to possibly correct diastolic dysfunction, we hypothesized that expression of the Ca 2+ binding protein parvalbumin in cardiac myocytes would lead to increased rates of Ca 2+ sequestration and mechanical relaxation. Parvalbumin, which is normally absent in cardiac tissue, is known to act as a soluble relaxing factor in fast skeletal muscle fibers by acting as a delayed Ca 2+ sink. As a test of the hypothesis, gene transfer was used to express parvalbumin in isolated adult cardiac myocytes. We report here that expression of parvalbumin dramatically increases the rate of Ca 2+ sequestration and the relaxation rate in normal cardiac myocytes. Importantly, parvalbumin fully restored the relaxation rate in diseased cardiac myocytes isolated from an animal model of human diastolic dysfunction. These findings indicate that parvalbumin gene transfer offers unique potential as a possible direct treatment for diastolic dysfunction in failing hearts.

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  • PV increases the rate of calcium sequestration, lowers presynaptic calcium levels, modulates short-term synaptic plasticity, and prevents cumulative facilitation.

    “PV increases the rate of Ca 2+ sequestration, reduces presynaptic Ca 2+ levels, modulates short-term synaptic plasticity, and prevents cumulative facilitation (Fig. 1), [67,68].”

    From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [68]

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Authors
Wahr, P. A., Michele, D. E., & Metzger, J. M.
Affiliations
University of Michigan (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-10-12
Volume
96
Issue
21
Pages
11982-11985
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.21.11982
PMC
PMC18398
OpenAlex
W2065503803
Cited by
66
References
22
Citations by year
2024: 1 · 2022: 2 · 2020: 3 · 2019: 1 · 2014: 1 · 2013: 3 · 2012: 5
FWCI
2.42
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
parvalbumin, diastolic dysfunction, heart failure, calcium sequestration, cardiomyocytes, gene transfer, calcium-binding proteins, mechanical relaxation, cardiac gene therapy
MeSH terms
Animals, Calcium, Cells, Cultured, Diastole, Disease Models, Animal, Female, Heart Failure, Hypothyroidism, Myocardium, Parvalbumins, Sarcomeres, Time Factors, Blotting, Western, Rats, Sprague-Dawley, Gene Transfer Techniques, Rats

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