UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Proteomic Analysis of the Myocardium in Hypertrophic Obstructive Cardiomyopathy

Coats, CJ; Heywood, WE; Virasami, A; Ashrafi, N; Syrris, P; dos Remedios, C; Treibel, TA; ... Elliott, PM; + view all (2018) Proteomic Analysis of the Myocardium in Hypertrophic Obstructive Cardiomyopathy. Circulation: Genomic and Precision Medicine , 11 (12) , Article e001974. 10.1161/CIRCGEN.117.001974. Green open access

[img]
Preview
Text
Ashrafi_MAIN MANUSCRIPT_CIRCCVG2017001974R2_13.11.18.pdf - Accepted version

Download (617kB) | Preview

Abstract

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 post genomic phenotype. Methods: Label-free proteomic analysis was used initially to compare protein profiles in myocardial samples from eleven patients with HCM undergoing surgical myectomy with control samples from six 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 (MRM) based triple quadrupole mass spectrometry. Results: In this exploratory study, 1586 proteins were identified with 151 proteins differentially expressed in HCM samples compared to controls (p<0.05). Protein expression profiling showed that many proteins identified in the initial discovery study were associated with metabolism, muscle contraction, calcium regulation and oxidative stress. Proteins down-regulated in HCM versus controls included creatine kinase M-type, Fructose-bisphosphate aldolase A and phosphoglycerate mutase (p<0.001). Proteins up-regulated in HCM included lumican, carbonic anhydrase 3, desmin, alpha actin skeletal and four and half LIM domain protein 1 (p<0.01). Myocardial lumican concentration correlated with left atrial area (rho 0.34, p=0.015), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (P=0.03) and the presence of a pathogenic sarcomere mutation (p=0.04). Conclusion: 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.

Type: Article
Title: Proteomic Analysis of the Myocardium in Hypertrophic Obstructive Cardiomyopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCGEN.117.001974
Publisher version: https://doi.org/10.1161/CIRCGEN.117.001974
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: fibrosis, hypertrophy, proteome, cardiomyopathies
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Genetics and Genomic Medicine Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Pop, Policy and Practice Prog
URI: https://discovery.ucl.ac.uk/id/eprint/10064848
Downloads since deposit
14Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item