Weighted gene coexpression network analysis reveals negative regulation of maximum left ventricular wall thickness by carboxylesterase 1 and cathepsin C in hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients was extracted from the Gene Expression Omnibus (GEO) database and analyzed by weighted gene co-expression network analysis (WGCNA). A total of 31 co-expression modules were identified. The co-expression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packet in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was down regulated in HCM tissues, and negatively correlated with Maxi LVWT. We further verified the above conclusion in clinical samples from HCM patients. We found the expression of CES1 and CTSC was down regulated in HCM tissues, and negatively correlated with Maxi LVWT. The above conclusion was further verified in clinical samples from HCM patients. In summary, the study suggests that CES1 and CTSC negatively regulate development of HCM and have potential as a therapeutic and diagnostic target for HCM.