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 dos Remedios; Joseph J. Maleszewski; Steve R. Ommen; Joseph A. Dearani; Michael J. Ackerman

doi:10.1038/s41598-023-40795-1

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 dos Remedios, Joseph J. Maleszewski, Steve R. Ommen, Joseph A. Dearani, Michael J. Ackerman

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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.

Original language	English (US)
Article number	14341
Journal	Scientific reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-40795-1
State	Published - Dec 2023

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Garmany, R., Bos, J. M., Dasari, S., Johnson, K. L., Tester, D. J., Giudicessi, J. R., dos Remedios, C., Maleszewski, J. J., Ommen, S. R., Dearani, J. A., & Ackerman, M. J. (2023). Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy. Scientific reports, 13(1), Article 14341. https://doi.org/10.1038/s41598-023-40795-1

Garmany, R, Bos, JM, Dasari, S, Johnson, KL, Tester, DJ, Giudicessi, JR, dos Remedios, C, Maleszewski, JJ, Ommen, SR, Dearani, JA & Ackerman, MJ 2023, 'Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy', Scientific reports, vol. 13, no. 1, 14341. https://doi.org/10.1038/s41598-023-40795-1

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title = "Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy",

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 (HCMSarc) present earlier and with more severe disease than those with a negative genetic test (HCMNeg). 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 HCMSarc, 8 HCMNeg, and 7 control samples. There were 243 proteins differentially expressed and 257 proteins differentially phosphorylated between HCMSarc and HCMNeg. About 90% of pathways altered between genotypes were in disease-related pathways and HCMSarc showed enhanced proteomic and phosphoproteomic alterations in these pathways. Thus, we show HCMSarc has enhanced proteomic and phosphoproteomic dysregulation observed which may contribute to the more severe disease phenotype.",

author = "Ramin Garmany and Bos, {J. Martijn} and Surendra Dasari and Johnson, {Kenneth L.} and Tester, {David J.} and Giudicessi, {John R.} and {dos Remedios}, Cristobal and Maleszewski, {Joseph J.} and Ommen, {Steve R.} and Dearani, {Joseph A.} and Ackerman, {Michael J.}",

note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",

year = "2023",

month = dec,

doi = "10.1038/s41598-023-40795-1",

language = "English (US)",

volume = "13",

journal = "Scientific reports",

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AU - Garmany, Ramin

AU - Bos, J. Martijn

AU - Dasari, Surendra

AU - Johnson, Kenneth L.

AU - Tester, David J.

AU - Giudicessi, John R.

AU - dos Remedios, Cristobal

AU - Maleszewski, Joseph J.

AU - Ommen, Steve R.

AU - Dearani, Joseph A.

AU - Ackerman, Michael J.

PY - 2023/12

Y1 - 2023/12

N2 - 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 (HCMSarc) present earlier and with more severe disease than those with a negative genetic test (HCMNeg). 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 HCMSarc, 8 HCMNeg, and 7 control samples. There were 243 proteins differentially expressed and 257 proteins differentially phosphorylated between HCMSarc and HCMNeg. About 90% of pathways altered between genotypes were in disease-related pathways and HCMSarc showed enhanced proteomic and phosphoproteomic alterations in these pathways. Thus, we show HCMSarc has enhanced proteomic and phosphoproteomic dysregulation observed which may contribute to the more severe disease phenotype.

AB - 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 (HCMSarc) present earlier and with more severe disease than those with a negative genetic test (HCMNeg). 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 HCMSarc, 8 HCMNeg, and 7 control samples. There were 243 proteins differentially expressed and 257 proteins differentially phosphorylated between HCMSarc and HCMNeg. About 90% of pathways altered between genotypes were in disease-related pathways and HCMSarc showed enhanced proteomic and phosphoproteomic alterations in these pathways. Thus, we show HCMSarc has enhanced proteomic and phosphoproteomic dysregulation observed which may contribute to the more severe disease phenotype.

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

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