通过选择性改变肌球蛋白或肌钙蛋白活性来增强心脏收缩的不同机制。

Singh Rohit R, Slater Rebecca E, Wang Jinghong, Wang Chen, Guo Qi, Motani Alykhan S, Hartman James J, Sadayappan Sakthivel, Ason Brandon L

Amgen Research, Department of Cardiometabolic Disorders, Amgen, South San Francisco, California, USA.

Heart, Lung and Vascular Institute, Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio, USA.

JACC Basic Transl Sci. 2022 Sep 7;7(10):1021-1037. doi: 10.1016/j.jacbts.2022.04.013. eCollection 2022 Oct.

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.

调节肌节收缩性代表了一种通过直接靶向肌节的粗肌丝和细肌丝蛋白来增强心肌收缩从而治疗心力衰竭的新治疗机会。本研究比较了两种小分子（M和T）对整体心肌力学的影响，这两种小分子分别选择性改变肌球蛋白粗肌丝（M）或肌钙蛋白细肌丝（T）的活性。本研究揭示了与M和T用于增加收缩力产生的机制相关的关键差异，并表明靶向肌节内不同的蛋白质可能会导致不同的治疗效果。