Abstract
Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous condition with about half of cases remaining genetically elusive or non-genetic in origin. HCM patients with a positive genetic test (HCM(Sarc)) present earlier and with more severe disease than those with a negative genetic test (HCM(Neg)). We hypothesized these differences may be due to and/or reflect proteomic and phosphoproteomic differences between the two groups. TMT-labeled mass spectrometry was performed on 15 HCM(Sarc), 8 HCM(Neg), and 7 control samples. There were 243 proteins differentially expressed and 257 proteins differentially phosphorylated between HCM(Sarc) and HCM(Neg). About 90% of pathways altered between genotypes were in disease-related pathways and HCM(Sarc) showed enhanced proteomic and phosphoproteomic alterations in these pathways. Thus, we show HCM(Sarc) has enhanced proteomic and phosphoproteomic dysregulation observed which may contribute to the more severe disease phenotype.