December 3, 2019Scientific ReportsOpen Access

Phosphomimetic cardiac myosin-binding protein C partially rescues a cardiomyopathy phenotype in murine engineered heart tissue

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Why the study?

cMyBP-C phosphorylation is lower in septal myectomies of HCM patients than non-failing hearts, prompting comparison of phosphomimetic versus wild-type cMyBP-C gene transfer.

Does phosphomimetic cMyBP-C gene transfer rescue the cardiomyopathy phenotype better than wild-type cMyBP-C in a murine engineered heart tissue model of HCM?

Population

Engineered heart tissues generated from a mouse model carrying a Mybpc3 mutation

Comparison

Phosphomimetic (D282) vs wild-type (S282) cMyBP-C gene transfer

Design

In vitro experimental study

Authors

ADAlexander DutschDeutsches Herzzentrum München PWPaul J.M. WijnkerHeart Failure / Cardiomyopathy SSSaskia SchlossarekUniversität Hamburg

Discussion

Member takes

Implication

Should not yet change HCM management; extends preclinical data favoring wild-type over phosphomimetic cMyBP-C gene transfer.

Structured PICO

Does phosphomimetic cMyBP-C gene transfer rescue the cardiomyopathy phenotype better than wild-type cMyBP-C in a murine engineered heart tissue model of HCM?

Population

Engineered heart tissues (EHTs) generated from a mouse model carrying a Mybpc3 mutation (KI) representing hypertrophic cardiomyopathy (HCM)

Intervention

Adeno-associated virus-mediated gene transfer of phosphomimetic (D282) cMyBP-C

Comparator

Adeno-associated virus-mediated gene transfer of wild-type (S282) cMyBP-C, and untreated KI EHTs / WT EHTs

Outcome

Rescue of the HCM phenotype (including Mybpc3 mRNA and protein levels, spontaneous contractions, maximal force, sensitivity to external Ca2+, and gene expression)surrogate

Wild-type (S282) cMyBP-C gene transfer is more effective than phosphomimetic (D282) cMyBP-C at normalizing force-calcium relationships and gene expression in a murine engineered heart tissue model of hypertrophic cardiomyopathy.

Limitations

In vitro model
Unclear to what extent the results apply to human HCM

Cite This Study

Dutsch et al. (2019) studied this question.

synapsesocial.com/papers/69d570b675589c71d767de79 https://doi.org/10.1038/s41598-019-54665-2

Topics

Hypertrophic cardiomyopathy

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Phosphomimetic cardiac myosin-binding protein C partially rescues a cardiomyopathy phenotype in murine engineered heart tissue

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Topics

Phosphomimetic cardiac myosin-binding protein C partially rescues a cardiomyopathy phenotype in murine engineered heart tissue

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Topics

Also Consider