Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective

Tyrosine kinase inhibitors (TKIs) have transformed cancer therapy but are associated with significant cardiovascular risks, including hypertension and heart failure. Here, we demonstrate that endothelial dysfunction driven by impaired mechanotransduction underlies TKI-induced hypertension and long-term cardiac dysfunction. Overall design: COs were generated using iPSC-CMs alone or in combination with iPSC-ECs. For co-culture organoids, iPSC-CMs and iPSC-ECs were dissociated using TrypLE Express (Sigma) and mixed at a 70:30 ratio (CM:EC).