Cyclic mechanical stretch of neonatal rat ventricular myocytes induced significant transcriptomic changes, with 1542 differentially expressed genes at 48 hours, highlighting Nrf2 and let-7 miRNAs.
Mechanical stretch of neonatal rat ventricular myocytes induces time-dependent transcriptomic changes, highlighting Nrf2, interferon regulatory transcription factors, and the let-7 miRNA family as key regulators of the hypertrophic gene program.
p-value: p=<0.05
Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by mechanical stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P < 0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic mechanical stretch. We used Ingenuity Pathway Analysis to predict functional pathways and upstream regulators of differentially expressed genes in order to identify regulatory networks that may lead to mechanical stretch induced hypertrophic growth of cardiomyocytes. We also performed micro (miRNA) expression profiling of stretched NRVMs, and identified that a total of 8 and 87 miRNAs were significantly (P < 0.05) altered by 1-12 and 24-48 hours of mechanical stretch, respectively. Finally, through integration of miRNA and mRNA data, we predicted the miRNAs that regulate mRNAs potentially leading to the hypertrophic growth induced by mechanical stretch. These analyses predicted nuclear factor-like 2 (Nrf2) and interferon regulatory transcription factors as well as the let-7 family of miRNAs as playing roles in the regulation of stretch-regulated genes in cardiomyocytes.
Rysä et al. (Mon,) conducted a other in Cardiac hypertrophy (in vitro model). Cyclic mechanical stretch vs. Unstretched control cells was evaluated on Differentially expressed genes (>1.5-fold change) (p=<0.05). Cyclic mechanical stretch of neonatal rat ventricular myocytes induced significant transcriptomic changes, with 1542 differentially expressed genes at 48 hours, highlighting Nrf2 and let-7 miRNAs.