Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy
Ramin Garmany, J. Martijn Bos, Surendra Dasari, Kenneth L. Johnson, David J. Tester, John R. Giudicessi, Cristobal G. dos Remedios, Joseph J. Maleszewski, Steve R. Ommen, Joseph A. Dearani, Michael J. Ackerman
Abstract
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.