A systems and translational approach to titin dynamics in HFpEF (B04)

巨大的肌联蛋白形成肌节的弹性骨架。它被广泛剪接和磷酸化以调节健康和疾病中的心脏充盈。在这里，我们将结合联合收割机我们的遗传与介入动物模型和人类工程心脏组织解剖肌联蛋白的心脏生长，代谢和填充的贡献，以及它与保留射血分数心力衰竭（HFpEF）。我们专注于肌联蛋白的生物力学和亚型表达在男性与女性将有助于提高HFpEF的机械理解，舒张功能障碍的评估，并适应肌联蛋白为基础的刚度作为靶向治疗的基础。

The giant protein titin forms the elastic backbone of the sarcomere. It is extensively spliced and phosphorylated to adjust cardiac filling in health and disease. Here, we will combine our genetic with interventional animal models and human engineered heart tissue to dissect titin’s contribution to cardiac growth, metabolism, and filling and its relation to heart failure with preserved ejection fraction (HFpEF). Our focus on titin biomechanics and isoform expression in male versus female will contribute to an improved mechanistic understanding of HFpEF, assessment of diastolic dysfunction, and the adaptation of titin based stiffness as a basis for targeted therapy.