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October 25, 2018Frontiers in PhysiologyOpen Access

Transcriptome Analysis of Cardiac Hypertrophic Growth in MYBPC3-Null Mice Suggests Early Responders in Hypertrophic Remodeling

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Key result

Transcriptome analysis of cMyBP-C-null mice revealed prehypertrophic upregulation of Xirp2 (2.87-fold) and Zbtb16 (2.40-fold), suggesting early dysregulation of mechanosensing pathways in HCM.

Population

cMyBP-C-/- mouse model of hypertrophic cardiomyopathy (HCM) and wild type (WT) mice (n=7 each)

Comparison

Microarray analysis on left ventricles at… vs Wild type (WT) mice

Design

Preclinical

Follow-up

Postnatal day 9

Authors

EFEmily T. FarrellUniversity of Wisconsin–MadisonAAAnnie E. ArmstrongUniversity of Wisconsin–MadisonAGAdrian C. GrimesUniversity of Wisconsin–Madison

Discussion

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Implication

Hypothesis-generating in cMyBP-C-null mice; extends preclinical insights into early HCM mechanosensing but requires human validation before clinical relevance.

Structured PICO

P
Population
28 male wild-type and cMyBP-C-null mice evaluated at postnatal days 1 and 9 to identify early genetic mediators of hypertrophic cardiomyopathy.
E
Exposure
Microarray analysis on left ventricles at postnatal day (PND) 1 and PND 9
C
Comparator
Wild type (WT) mice
O
Outcome
Gene expression changes (>2 fold) differentiating physiologic and pathophysiologic hypertrophic growthsurrogate

Transcriptome analysis in a mouse model of HCM reveals early prehypertrophic dysregulation of mechanosensing pathways and potassium channels, specifically highlighting Xirp2 and Zbtb16.

Limitations

  • Microarray is less sensitive than newer methods such as RNA Seq, potentially missing some pathway dysregulation.

Cite This Study

Farrell et al. (2018) studied Hypertrophic cardiomyopathy (HCM) (n=28). cMyBP-C genetic ablation (cMyBP-C-/-) vs. Wild-type (WT) littermates was evaluated on Differential gene expression (transcriptome analysis). Transcriptome analysis of cMyBP-C-null mice revealed prehypertrophic upregulation of Xirp2 (2.87-fold) and Zbtb16 (2.40-fold), suggesting early dysregulation of mechanosensing pathways in HCM.

synapsesocial.com/papers/6a204a91f8fff11fb92ed0d2https://doi.org/10.3389/fphys.2018.01442
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Also Consider

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

  1. 1Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations.1994 · 226 citations
  2. 2Differential Expression of Voltage-Gated K + Channel Subunits in Adult Rat Heart1995 · 253 citations
  3. 3Increased Postnatal Cardiac Hyperplasia Precedes Cardiomyocyte Hypertrophy in a Model of Hypertrophic Cardiomyopathy2017 · 23 citations
  4. 4The Transitional Junction: A New Functional Subcellular Domain at the Intercalated Disc2006 · 80 citations
  5. 5In Vivo Cardiac Myosin Binding Protein C Gene Transfer Rescues Myofilament Contractile Dysfunction in Cardiac Myosin Binding Protein C Null Mice2012 · 42 citations