Pathological
cardiac hypertrophy is the main predecessor of
heart failure. Its pathology is sophisticated, and its progression is associated with multiple cellular processes. To explore new therapeutic approaches, more precise examination of cardiomyocyte subtypes and involved biological processes is required in response to hypertrophic stimuli. Mitochondria and the endoplasmic reticulum (ER) are two crucial organelles associated with the progression of
cardiac hypertrophy and are connected through junctions known as mitochondria-associated endoplasmic reticulum membranes (MAMs). Although MAM genes are altered in
cardiac hypertrophy, the importance of MAMs in
cardiac hypertrophy and the expression pattern of MAMs in certain cardiac cell types require a comprehensive analysis. In this study, we analyzed the temporal expression of MAM
proteins in the process of
cardiac hypertrophy and observed that MAM-related
proteins preferentially accumulated in cardiomyocytes at the initial stage of
cardiac hypertrophy and underwent a gradual decline, which was synchronized with the proportion of two cardiomyocyte subtypes (CM2 and CM3). Meanwhile, these subtypes went through a functional switch during
cardiac hypertrophy. Trajectory analysis suggested that there was a differentiation trajectory of cardiomyocyte subtypes from high to low MAM
protein expression. Distinct regulon modules across different cardiomyocyte cell types were revealed by transcriptional regulatory network analysis. Furthermore, scWGCNA revealed that MAM-related genes were clustered into a module that correlated with
diabetic cardiomyopathy. Altogether, we identified cardiomyocyte subtype transformation and the potential critical
transcription factors involved, which may serve as therapeutic targets in combating
cardiac hypertrophy.