The effect of substrate stiffness on cardiac performance

人类心肌的硬度随着年龄的增长而增加，这与心室病变的风险增加有关，如保留射血分数的心力衰竭（HFpEF），特别是在存在合并症的老年人中。细胞外基质蛋白，尤其是胶原沉积的增加，被认为是导致心脏硬度增加的原因。然而，心肌僵硬增加的机制尚不完全清楚。本项目的目的是在体外模拟增加的基质刚度，并研究基质刚度对诱导多能心肌细胞生物学、电生理和代谢的影响。底物硬度对心肌细胞性能的影响将通过收缩性测量和电生理分析来评估。

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.