In PLN-R14del mice, SR structure restoration, rather than calcium cycling, is the dominant effector of PLN-ASO treatment
PLN-ASO treatment demonstrated a dose-dependent restoration of SR organization and a concomitant increase in lifespan in PLN-R14del mice. The enhanced SR calcium uptake in PLN-R14del mice suggests a partial loss of inhibitory function, limiting ASO therapy's effects on calcium dynamics. This implies that PLN-ASO therapy acts predominantly via restoration of SR structure in PLN-R14del cardiomyopathy.
Authors
- David Janzén (ORCID: https://orcid.org/0000-0002-4134-3849)
- Daniela Später (ORCID: https://orcid.org/0000-0002-5398-1784)
- Adam E. Mullick (ORCID: https://orcid.org/0000-0003-4600-961X)
- Carl Amilon (ORCID: https://orcid.org/0000-0001-5409-7221)
- Dieter A. Kubli (ORCID: https://orcid.org/0000-0001-7970-4075)
- Kenny M. Hansson (ORCID: https://orcid.org/0000-0003-0448-5140)
- Tim R. Eijgenraam (ORCID: https://orcid.org/0000-0001-8843-9656)
- Vivian Oliveira Nunes Teixeira (ORCID: https://orcid.org/0000-0002-1987-7158)
- Liu Sun (ORCID: https://orcid.org/0000-0003-4800-8784)
- Peter van der Meer (ORCID: https://orcid.org/0000-0002-9705-4413)
- Herman H W Silljé
Institutions
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- Ionis Pharmaceuticals (United States) (US)
- AstraZeneca (South Korea) (KR)
- AstraZeneca (Finland) (FI)
- AstraZeneca (Sweden) (SE)
- AstraZeneca (United States) (US)
Publication Details
- Journal
- Cardiovascular Research
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1093/cvr/cvaf156
- Citations
- 2
- Primary Topic
- Cardiovascular Effects of Exercise
- Type
- article
- Field-Weighted Citation Impact
- 2.78
Funders
- AstraZeneca
- Ionis Pharmaceuticals
- Fondation Leducq
- ZonMw
- China Scholarship Council
- Universitair Medisch Centrum Groningen