Heart failure (HF) represents a major health problem as it causes high prevalence and mortality worldwide. In HF, the cardiac contractile machine is weakened under the low pH conditions experienced. Decreases in intracellular pH have been shown to directly affect the structure of the contractile protein cardiac troponin I. So far, no treatment has yet convincingly shown to improve outcomes in patients with HF and they experience worsening symptoms, frequent admission to hospital, and premature death.
The aim of my research is to use the cyclic peptide Trop_L01 produced using the Random non-standard Peptide Integrated Discovery (RaPID) approach for the development of drugs to treat heart failure. The function of this peptide is to enhance the intracellular interaction between cardiac troponin I and cardiac troponin C in order to generate stronger myocardial contraction.
To assess the effect of Trop_L01 on the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), I recorded videos of these cells 30 min and 60 min after addition of the peptide and controls and analysed time-to-peak contractility and relaxation time using the software Musclemotion. Thus, I used a fluorescent imaging plate reader (FLIPR) to examine the effect of Trop_L01 on calcium transients in hiPSC-CMs. Remarkably, Trop_L01 was found to enhance contractility by decreasing time to peak and relaxation time at both 30 min and 60 min after peptide addition. Trop_L01 does not affect calcium amplitude or beating activity compared to baseline values. We conclude that Trop_L01 improves the contractility of hiPSC-CMs.