Analysis by RNA-seq of the transcriptional profile of left ventricles of WT, CST-KO and CST-KO+CST treated mice

Hypertension is a critical risk factor for heart failure (HF), with metabolic inflexibility playing a pivotal role. Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) exerts hypotensive and cardioprotective effects, nonetheless CST’s effect on cardiac metabolism remains unexplored. Our transcriptomic approach coupled with filtering through Boolean implication relationships identified a set of gene signatures (fibroblast, cardiomyocyte, and macrophage) that were altered in CST knockout (CST-KO) mice and restored after CST supplementation. These gene signatures obtained from our in vivo experiments corroborated with publicly available HF patient datasets.