| Autor: |
Caroline J. Coats, Wendy E. Heywood, Alex Virasami, Nadia Ashrafi, Petros Syrris, Cris dos Remedios, Thomas A. Treibel, James C. Moon, Luis R. Lopes, Christopher G.A. McGregor, Michael Ashworth, Neil J. Sebire, William J. McKenna, Kevin Mills, Perry M. Elliott |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Circulation: Genomic and Precision Medicine. 11 |
| ISSN: |
2574-8300 |
| DOI: |
10.1161/circgenetics.117.001974 |
| Popis: |
Background: Hypertrophic cardiomyopathy (HCM) is characterized by a complex phenotype that is only partly explained by the biological effects of individual genetic variants. The aim of this study was to use proteomic analysis of myocardial tissue to explore the postgenomic phenotype. Methods: Label-free proteomic analysis was used initially to compare protein profiles in myocardial samples from 11 patients with HCM undergoing surgical myectomy with control samples from 6 healthy unused donor hearts. Differentially expressed proteins of interest were validated in myocardial samples from 65 unrelated individuals (HCM [n=51], controls [n=7], and aortic stenosis [n=7]) by the development and use of targeted multiple reaction monitoring-based triple quadrupole mass spectrometry. Results: In this exploratory study, 1586 proteins were identified with 151 proteins differentially expressed in HCM samples compared with controls ( P P P P =0.015), late gadolinium enhancement on cardiac magnetic resonance imaging ( P =0.03) and the presence of a pathogenic sarcomere mutation ( P =0.04). Conclusions: The myocardial proteome of HCM provides supporting evidence for dysregulation of metabolic and structural proteins. The finding that lumican is raised in HCM hearts provides insight into the myocardial fibrosis that characterizes this disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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