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March 7, 2020Basic Research in CardiologyOpen Access

CRISPLD1: a novel conserved target in the transition to human heart failure

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Why the study?

Heart failure is a major health problem, but data from patients at the compensated disease stage transitioning to failure are lacking despite extensive animal studies.

Does CRISPLD1 knockout alter calcium cycling and transcriptomic profiles in human-induced pluripotent stem cell-derived cardiomyocytes?

Population

Myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure, and transverse aortic constriction mice

Comparison

Compensated hypertrophy vs moderate heart failure

Design

Transcriptomic and comparative sequencing translational study

Authors

SKSara KhadjehGerman Centre for Cardiovascular ResearchVHVanessa HindmarshUniversitätsmedizin GöttingenFWFrederike WeberForschungszentrum Jülich

Discussion

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Implication

CRISPLD1 knockout enhances calcium transients in hiPSC-CMs; leaves open its therapeutic targeting in heart failure pending in vivo validation.

Structured PICO

Does CRISPLD1 knockout alter calcium cycling and transcriptomic profiles in human-induced pluripotent stem cell-derived cardiomyocytes?

P
Population
Human myocardium biopsies from aortic stenosis patients (compensated hypertrophy n=5, moderate HF n=5), non-failing controls (n=4), and terminal HF (n=6); transverse aortic constriction (TAC) mouse model (1wTAC n=4, 8wTAC n=5, sham); and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
I
Intervention
CRISPR/Cas9-mediated knockout of CRISPLD1
C
Comparator
Isogenic wild-type (WT) hiPSC-CMs
O
Outcome
Calcium transient (CaT) amplitude, rise time, and decay, and transcriptomic/proteomic changessurrogate

CRISPLD1 is a novel conserved gene upregulated in the transition to heart failure that acts as a negative regulator of calcium cycling in human cardiomyocytes.

Limitations

  • Small number of human myocardial AS samples available (five CH, five moderate HF, four controls)

Cite This Study

Khadjeh et al. (2020) studied this question.

synapsesocial.com/papers/6a822167fc3df235bc877610https://doi.org/10.1007/s00395-020-0784-4

Topics

Heart failureHFrEF treatment
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Transcriptomal analysis of failing and nonfailing human hearts2003 · 88 citations
  2. 2A Secretion Trap Screen in Yeast Identifies Protease Inhibitor 16 as a Novel Antihypertrophic Protein Secreted From the Heart2007 · 61 citations
  3. 3Genomic analysis reveals poor separation of human cardiomyopathies of ischemic and nonischemic etiologies2008 · 24 citations
  4. 4Heart Failure: Diagnosis, Management and Utilization2016 · 421 citations
  5. 5Heart Failure: Preventing Disease and Death Worldwide2014 · 1,719 citations