Transcriptomic analysis of Serinc2 -dependent alterations during Phenylephrine-induced Cardiomyocyte Hypertrophy
The study aims to explore the role of Serinc2 in the regulation of cardiac hypertrophy, a condition characterized by the enlargement of cardiomyocytes and increased protein synthesis. The mechanistic target of rapamycin complex 1 (mTORC1) plays a critical role in controlling protein synthesis and cell growth in response to changes in cellular nutrients and energy levels. we discovered that Serinc2 expression is reduced in the cardiac hypertrophic induced by transverse aortic constriction (TAC). Through RNA sequencing, we identified a pro-hypertrophic transcriptomic profile following Serinc2 knockdown, suggesting a connection between Serinc2, amino acids, mTOR signaling, and lysosomal function. Serinc2 deficiency was found to enhance mTORC1 activity and increase protein synthesis. This was confirmed in Serinc2-deficient mice subjected to TAC surgery, which showed increased phosphorylation of mTORC1. Importantly, inhibiting mTORC1 signaling through amino acid deprivation halted the progression of cardiac hypertraphy. Therefore, Serinc2 represents a potential therapeutic target for preventing pathological heart failure by suppressing excessive protein synthesis under stress.