Heart failure & cardiomyopathies
Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D
Authors' conclusion
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.
Study context
- Population
- Patients with HF receiving left ventricular assist device (LVAD) as a bridge to transplant
- Comparison
- LVAD responders vs nonresponders
- Respondersn = 10
- Nonrespondersn = 9reference
- Outcome
- Molecular signatures of recovery
Methodological detailspaired pre-LVAD and post-LVAD myocardial samples, bulk RNA sequencing, TMT proteomics and phosphoproteomics, primary rat cardiomyocytes and human engineered heart tissues
- Paired pre-LVAD and post-LVAD myocardial samples
- Bulk RNA sequencing, TMT proteomics and phosphoproteomics
- Primary rat cardiomyocytes and human engineered heart tissues
Main finding
As reported in the abstract
- Alternative RNA splicing was the leading pathway associated with a favorable response to LVAD
- Responders had increased RNA splicing factor expression and unique gene splice variant expression vs nonresponders
- Increased inclusion of CAMK2D exon 14 (nuclear variant CAMK2D-B) inversely correlated with functional recovery
- Nonresponders displayed hyperphosphorylation near the nuclear localization signal in CAMK2D-B
- Nuclear localization signal phosphorylation prevented adrenergic stress-dependent nuclear targeting of CAMK2D-B
- Cytoplasm-restricted CAMK2D-B uniquely remodeled the phosphoproteome of rat cardiomyocytes and blunted calcium transients in engineered heart tissues
Original publication
Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D. Circulation. Published 5 January 2026. doi:10.
Summarised from the published abstract; every number is checked against it