Key result
Cyclic mechanical stretch of hiPSC-CMs induced distinct hypertrophic changes in gene expression, establishing them as a valuable in vitro model for studying human cardiomyocyte hypertrophy.
Why the study?
Previous hypertrophy studies using neonatal rat ventricular myocytes and animal models revealed genes and pathways associated with mechanical load, but these models are not directly applicable to humans.
hiPSC-CMs subjected to mechanical stretch serve as a relevant human in vitro model for studying left ventricular hypertrophy.
hiPSC-CM stretch model extends in vitro LVH tools; leaves open clinical translation.
Left ventricular hypertrophy, characterized by hypertrophy of individual cardiomyocytes, is an adaptive response to an increased cardiac workload that eventually leads to heart failure. Previous studies using neonatal rat ventricular myocytes (NRVMs) and animal models have revealed several genes and signaling pathways associated with hypertrophy and mechanical load. However, these models are not directly applicable to humans. Here, we studied the effect of cyclic mechanical stretch on gene expression of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using RNA sequencing. hiPSC-CMs showed distinct hypertrophic changes in gene expression at the level of individual genes and in biological processes. We also identified several differentially expressed genes that have not been previously associated with cardiomyocyte hypertrophy and thus serve as attractive targets for future studies. When compared to previously published data attained from stretched NRVMs and human embryonic stem cell-derived cardiomyocytes, hiPSC-CMs displayed a smaller number of changes in gene expression, but the differentially expressed genes revealed more pronounced enrichment of hypertrophy-related biological processes and pathways. Overall, these results establish hiPSC-CMs as a valuable in vitro model for studying human cardiomyocyte hypertrophy. Non-standard Abbreviations and Acronyms ET-1, endothelin-1; GO, gene ontology; hESC-CM, human embryonic stem cell-derived cardiomyocyte; hiPSC, human induced pluripotent stem cell; hiPSC-CM, human induced pluripotent stem cell-derived cardiomyocyte; MAPK, mitogen-activated protein kinase; MEK1/2, mitogen-activated protein kinase kinase 1/2; NRVM, neonatal rat ventricular myocyte; PKC, protein kinase C; PBS, phosphate-buffered saline; RB+, RPMI 1640 supplemented with B-27; RB-, RPMI 1640 medium supplemented with B-27 without insulin; RT, room temperature; TF, transcription factor
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Pohjolainen et al. (2021) studied Left ventricular hypertrophy (in vitro model). Cyclic mechanical stretch vs. Unstretched control cells was evaluated on Differential gene expression (transcriptomics). Cyclic mechanical stretch of hiPSC-CMs induced distinct hypertrophic changes in gene expression, establishing them as a valuable in vitro model for studying human cardiomyocyte hypertrophy.
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