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January 23, 1998Circulation ResearchOpen Access

A Mutant Tropomyosin That Causes Hypertrophic Cardiomyopathy Is Expressed In Vivo and Associated With an Increased Calcium Sensitivity

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Population

2 familial hypertrophic cardiomyopathy patients carrying an Asp175Asn alpha-fast tropomyosin mutation and 2…

Comparison

Asp175Asn alpha-fast TM mutation vs Healthy control subjects lacking the mutant TM

Design

Preclinical

Authors

RBRoberto BottinelliHeart Failure / CardiomyopathyDCDomenico CovielloIstituto Giannina GasliniCRCharles RedwoodHeart Failure / Cardiomyopathy

Discussion

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Implication

Challenges hypothesis of primary contractile impairment in FHC; leaves open clinical relevance from animal data.

Key Points

  • This research aimed to determine whether a mutant alpha-fast tropomyosin is expressed in vivo and affects contractile function.
  • Samples were collected from vastus lateralis muscles of two patients with FHC and two healthy controls.
  • Gel electrophoresis and Western blot analyses were used to identify tropomyosin isoforms from muscle biopsies and single fibers.
  • Contractile properties of skinned muscle fibers were compared between FHC patients and healthy controls.
  • A faster-migrating tropomyosin band was detected in FHC patients, identified as the Asp175Asn alpha-fast TM.
  • Calcium sensitivity was significantly increased in muscle fibers with the mutant TM compared to those without it.
  • No significant differences in cooperativity, maximum force, and maximum shortening velocity were observed.

Structured PICO

P
Population
2 familial hypertrophic cardiomyopathy (FHC) patients carrying an Asp175Asn alpha-fast tropomyosin (TM) mutation and 2 healthy control subjects (n=4)
I
Intervention
Asp175Asn alpha-fast TM mutation
C
Comparator
Healthy control subjects lacking the mutant TM
O
Outcome
Expression of mutant TM and contractile parameters (calcium sensitivity, cooperativity, maximum force, and maximum shortening velocity) of single skinned muscle fiberssurrogate

The Asp175Asn alpha-fast TM mutation is expressed in vivo and increases calcium sensitivity, challenging the hypothesis that FHC mutations primarily induce contractile impairment.

Cite This Study

Bottinelli et al. (1998) studied this question.

synapsesocial.com/papers/6a1bf2fc27b545b111a93ee8https://doi.org/10.1161/01.res.82.1.106

Topics

Hypertrophic cardiomyopathy
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action.1996 · 136 citations
  2. 2Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy.1996 · 118 citations
  3. 3Human hTM alpha gene: expression in muscle and nonmuscle tissue.1988 · 47 citations
  4. 4Structural Aspects of Troponin-Tropomyosin Regulation of Skeletal Muscle Contraction1987 · 532 citations