Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy
Authors' conclusion
Human HCM demonstrates calcium mishandling through both genotype-specific and common pathways. Posttranslational activation of the CaMKII pathway is specific to sarcomere mutation-positive HCM, whereas sarcoplasmic endoplasmic reticular calcium ATPase 2 abundance and sarcoplasmic reticulum Ca uptake are depressed in both sarcomere mutation-positive and -negative HCM.
Study context
- Population
- Human hypertrophic cardiomyopathy (HCM) surgical myocardial samples
- Participants
- 25 / 10 / 8
- Comparison
- HCM with vs without sarcomere mutations vs control hearts
- Sarcomere-mutation HCMn = 25
- Mutation-negative HCMn = 10
- Controlsn = 8reference
- Outcome
- Calcium regulatory pathways (gene expression, protein levels, functional assays)
Main finding
As reported in the abstract
- CaMKII protein abundance increased only in sarcomere-mutation HCM
- P<0.001
- pT17-phospholamban 5.5-fold increased only in sarcomere-mutation HCM
- P=0.01
- Autophosphorylated CaMKII increased only in sarcomere-mutation HCM
- P<0.01
- SERCA2A mRNA reduced in HCM regardless of genotype; SERCA2/phospholamban protein ratio 45% reduced
- P=0.03
- 45Ca SERCA uptake velocity reduced in HCM regardless of genotype
- P=0.01
Original publication
Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy. Circulation. Published 29 September 2016. doi:10.
Summarised from the published abstract; every number is checked against it