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December 1, 2016Cell ReportsOpen Access

Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human β-Cardiac Myosin

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Key result

Early-onset HCM mutations D239N and H251N increase myosin motor function up to ~90% vs wild-type.

Population

Human β-cardiac myosin

Comparison

Early-onset hypertrophic cardiomyopathy… vs Wild-type human β-cardiac myosin

Design

Preclinical

Authors

AAArjun S. AdhikariCardiovascular Institute of the SouthKKKristina B. KooikerUniversity of WashingtonSSSaswata S. SarkarCytokinetics (United States)

Discussion

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Implication

Hypercontractility may underlie early-onset HCM; hypothesis-generating for myosin-targeted therapies pending human validation.

Structured PICO

P
Population
Human β-cardiac myosin
I
Intervention
Early-onset hypertrophic cardiomyopathy (HCM) mutations D239N and H251N
C
Comparator
Wild-type human β-cardiac myosin
O
Outcome
Molecular biomechanics including actin gliding velocity, intrinsic force, and ATPase activitysurrogate

Early-onset HCM mutations D239N and H251N lead to significant hyper-contractility by increasing fundamental biomechanical parameters of human β-cardiac myosin.

Cite This Study

Adhikari et al. (2016) studied Hypertrophic cardiomyopathy (HCM). Early-onset HCM mutations D239N and H251N vs. Wild-type myosin was evaluated on Actin gliding velocity, intrinsic force, and ATPase activity. Early-onset HCM mutations D239N and H251N significantly increased actin gliding velocity, intrinsic force, and ATPase activity by 20%-90% compared to wild-type human β-cardiac myosin.

synapsesocial.com/papers/6a08db3073760a4edcd6041bhttps://doi.org/10.1016/j.celrep.2016.11.040

Topics

Hypertrophic cardiomyopathy
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Also Consider

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

  1. 1Abnormal contractile properties of muscle fibers expressing beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy.1995 · 183 citations
  2. 2Chaperone-mediated folding and assembly of myosin in striated muscle2004 · 155 citations
  3. 3Understanding Cardiomyopathy Phenotypes Based on the Functional Impact of Mutations in the Myosin Motor2012 · 188 citations
  4. 4Hypertrophic cardiomyopathy-related β-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells2004 · 59 citations
  5. 5Hypertrophic and Dilated Cardiomyopathy: Four Decades of Basic Research on Muscle Lead to Potential Therapeutic Approaches to These Devastating Genetic Diseases2014 · 290 citations