Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy.

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.
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