4.6 Article

Distinct Mechanisms for Increased Cardiac Contraction Through Selective Alteration of Either Myosin or Troponin Activity

Journal

JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 7, Issue 10, Pages 1021-1037

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2022.04.013

Keywords

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Funding

  1. National Institutes of Health [R01 AR078001, R01 HL130356, R01 HL105826, R38 HL155775, R01 HL143490]

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This study compared the effects of two small molecules that alter the activity of sarcomere proteins on cardiac muscle mechanics. The results showed differences in the mechanism of contractile force generation, suggesting that targeting different proteins within the sarcomere may lead to different therapeutic outcomes.
Modulation of sarcomere contractility represents a new therapeutic opportunity for the treatment of heart failure by directly targeting the thick and thin filament proteins of the sarcomere to increase cardiac muscle contraction. This study compared the effect of 2 small molecules (M and T) that selectively alter myosin thick filament (M) or troponin thin filament (T) activity on overall cardiac muscle mechanics. This study revealed key differences related to the mechanism utilized by M and T to increase contractile force generation and suggests that targeting different proteins within the sarcomere may result in differentiating therapeutic profiles. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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