Our new paper entitled “Transcriptomics reveal stretched human pluripotent stem cell-derived cardiomyocytes as an advantageous hypertrophy model” has been accepted for publication in Journal of Molecular and Cellular Cardiology Plus. In this study, we established a hypertrophy model of stretched human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We analyse the transcriptomic changes of stretched hiPSC-CMs and compare those changes to previously reported models of cardiomyocyte hypertrophy.
Cardiomyocyte hypertrophy is a pathological condition, which may impair cardiac function and lead to heart failure. It is usually caused by increased workload of the heart, for example due to high blood pressure. This increased workload can be simulated in cell cultures by applying cyclic mechanical stretch to the cardiomyocytes. In our model, the stretch varies between mild (10% elongation of cardiomyocytes) and high (21% elongation) in two-second cycles reflecting the situation in overloaded beating heart. Although cardiomyocyte hypertrophy is widely studied, many of the studies rely on rodent cardiomyocytes or animal models. Since not all human hypertrophic signalling pathways exist in rodents and to reduce the use of experimental animals, we wanted to establish a human cardiomyocyte-based hypertrophy model.
Using RNA sequencing we characterised the transcriptomic profile of stretched hiPSC-CMs. The results revealed distinct hypertrophic changes in gene expression at the level of individual genes and in enriched biological processes. When compared to previously published models of stretched neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, hiPSC-CMs displayed more pronounced enrichment of hypertrophy-related biological processes and pathways. In addition, cardiomyocyte hypertrophy was confirmed by staining of the clinically used cardiac stress biomarker proBNP. These results establish cyclic mechanical stretching of hiPSC-CMs as a valuable in vitro model for studying human cardiomyocyte hypertrophy. The article is openly available at: https://doi.org/10.1016/j.jmccpl.2022.100020