Cardiac hypertrophy in human stem cells-derived cardiomyocytes : Biomarker identification and pathway analysis of endotheline-1 induced cardiac hypertrophy in human induced pluripotent stem cells-derived cardiomyocytes

Cardiac hypertrophy is when heart muscles thicken as an adaptive response to several stimuli. Prolonged pathological cardiac hypertrophy can lead to heart failure and severe cardiovascular diseases. Scientists have faced challenges in studying cardiac hypertrophy due to the lack of human cardiomyocytes available. Recently, hypertrophic model using human induced pluripotent stem cell-derived cardiomyocytes was introduced. In this study, expression profiles of in vitroendothelin-1 induced cardiac hypertrophy model were investigated at different time points. The study aimed to examine molecular pathways associated with cardiac hypertrophy, identify biomarker candidates for cardiac hypertrophy, and investigate if there were known pharmaceuticals that putatively are targeting the suggested candidate biomarkers. Using the Ingenuity pathway analysis (IPA) software, GRM1, NPPA, and STC1 gene were identified as biomarker candidates for cardiac hypertrophy model across all time points. More biomarker candidates unique to the cardiac hypertrophy-stages were also identified using IPA. In vivomicroarray data of hypertrophied heart profiles were also used to compare to the in vitro data and preliminarily validate the gene candidates identified by IPA. Four genes were identified by IPA and were presented in the in vivo data. IPA also revealed the in activation of specific pathways of the early-stage cardiac hypertrophy model. The result suggested that the molecular mechanisms of the in vitro cardiac hypertrophy model did not fully represent the actual hypertrophic condition of the heart. More research and validation are required to understand the underlying mechanism fully and potentially, in the future, utilize the identified genes as cardiac hypertrophy biomarkers