The effect of substrate stiffness on cardiac performance

作为衰老过程的一部分，人类心肌的硬度增加，这与心室病变（例如射血分数保留性心力衰竭（HFpEF））的风险较高相关，尤其是在存在合并症的老年人中。细胞外基质蛋白，特别是胶原蛋白的沉积增加被认为会导致心脏僵硬度增加。然而，心肌僵硬度增加的机制还不完全清楚。本项目的目的是在体外建立基质刚度增加的模型，并研究基质刚度对诱导多能心肌细胞生物学、电生理学和代谢的影响。将通过收缩力测量和电生理学测定来评估基底硬度对心肌细胞性能的影响。

The stiffness of the human myocardium increases as part of the ageing process, which is associated with a higher risk of ventricular pathologies such as heart failure with preserved ejection fraction (HFpEF), especially in elderly in the presence of co- morbidities. Increased deposition of extracellular matrix proteins, particularly collagens, are believed to drive increased cardiac stiffness. However, the mechanisms underlying increased myocardial stiffness are not entirely understood. The objectives of this project are to model increased matrix stiffness in vitro, and investigate the effects of matrix stiffness on induced pluripotent cardiomyocyte biology, electrophysiology and metabolism. The effect of substrate stiffness onto cardiomyocyte performance will be assessed by contractility measurements and electrophysiological assays.