A Cluster of Potential Molecular Contributors in Myocardial-Tissue-Derived In Situ Proteomic Profiling Mediate...

Myocardial hypertrophy is an adaptive response in the initial stage of heart failure (HF), which exacerbates HF by causing cardiac decompensation and impaired contractility. In proteomic analysis, 216 differentially expressed proteins were obtained in the RHD patients relative to normal controls, including 141 upregulated and 75 downregulated proteins. Among these candidate proteins, protein phosphatase 3 catalytic subunit alpha (PPP3CA), indolethylamine N-methyltransferase (INMT), a disintegrin and metalloproteinase 9 (ADAM9), and myosin light chain-2 (MYL2) exhibited significantly higher expression in the myocardial tissues from patients compared with controls. Moreover, bioinformatic analysis demonstrated that dysregulation of PPP3CA, INMT, ADAM9, and MYL2 may alter the expression of proteins involved in cell adhesion, gap junction coupling, and tight junction stability, weakening cell-cell contacts and disrupting intercellular homeostasis, ultimately facilitating myocardial hypertrophy. In the Angiotensin (Ang) II-induced myocardial hypertrophy model in AC16 cardiomyocytes, the protein expression of PPP3CA, ADAM9, and INMT was elevated. Furthermore, PPP3CA, ADAM9, and INMT were involved in Ang II-induced myocardial hypertrophy by upregulating the expression of smooth muscle α-actin, atrial natriuretic factor, and connective tissue growth factor. Our study identifies molecular alterations associated with the development of myocardial hypertrophy, which may provide insights into potential therapeutic strategies for RHD and subsequent heart failure.