Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D
This is the first study to integrate transcriptome, alternative transcriptome, proteome, and phosphoproteome analyses of heart samples from LVAD-supported patients to investigate myocardial recovery. We identified that increased expression and phosphorylation of the nuclear CAMK2D splice variant predicted poor outcomes. This phosphorylation restricted CAMK2D-B to the cytosol, leading to impaired cardiomyocyte calcium handling. These findings suggest that LVAD nonresponder patients may benefit from therapies that modulate subcellular localization of CAMK2D or inhibit its activity.
Authors
- Sarah G. Bruner (ORCID: https://orcid.org/0000-0001-7103-9664)
- Sharon Graw (ORCID: https://orcid.org/0000-0003-4577-1493)
- Christina Alamana (ORCID: https://orcid.org/0000-0003-4578-3638)
- Jason A. Burdick (ORCID: https://orcid.org/0000-0002-2006-332X)
- Peter M. Buttrick (ORCID: https://orcid.org/0000-0002-5692-2691)
- Christopher C. Ebmeier (ORCID: https://orcid.org/0000-0001-7940-6190)
- Dakota R. Hunt (ORCID: https://orcid.org/0000-0002-6621-5915)
- Luisa Mestroni (ORCID: https://orcid.org/0000-0003-1116-2286)
- LA Leinwand
- Abhishek P. Dhand (ORCID: https://orcid.org/0000-0002-1470-1081)
- Joseph C. Cleveland (ORCID: https://orcid.org/0000-0003-0535-4521)
- Thomas G. Martin (ORCID: https://orcid.org/0000-0002-1300-4890)
- Michael R. Bristow
- Amrut V. Ambardekar
- Matthew R.G. Taylor
Institutions
- University of Colorado Boulder (US)
- Bioengineering Center (RU)
- University of Colorado Anschutz Medical Campus (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Circulation
- Published
- 2026-01-05
- DOI
- https://doi.org/10.1161/circulationaha.125.075789
- Citations
- 1
- Primary Topic
- Mechanical Circulatory Support Devices
- Type
- article
- Field-Weighted Citation Impact
- 21.28