Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.

Embryonic signaling pathways exert stage-specific effects during cardiac development, yet the precise signals for proliferation or maturation remain elusive. To uncover the cues for proliferation, we performed a combinatory cell-cycle screen for insulin and glycogen synthase kinase-3 (GSK3) inhibition in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our analysis for proliferation, and subsequential downstream sarcomere development, gene expression analysis, and molecular interventions identified a temporal interplay between insulin/Akt/FOXO and CHIR99021/Wnt/GSK3/TCF signaling.

miR-24-3p secreted as extracellular vesicle cargo by cardiomyocytes inhibits fibrosis in human cardiac microtissues.

Background And Aims: Cardiac fibrosis in response to injury leads to myocardial stiffness and heart failure. At the cellular level, fibrosis is triggered by the conversion of cardiac fibroblasts (CF) into extracellular matrix-producing myofibroblasts. miR-24-3p regulates this process in animal models.

How microsimulation translates outcome estimates to patient lifetime event occurrence in the setting of heart valve disease.

Treatment decisions in healthcare often carry lifelong consequences that can be challenging to foresee. As such, tools that visualize and estimate outcome after different lifetime treatment strategies are lacking and urgently needed to support clinical decision-making in the setting of rapidly evolving healthcare systems, with increasingly numerous potential treatments. In this regard, microsimulation models may prove to be valuable additions to current risk-prediction models.