A network analysis to identify pathophysiological pathways distinguishing ischemic from non-ischemic heart failure

Sama, I. E. et al. (2020) A network analysis to identify pathophysiological pathways distinguishing ischemic from non-ischemic heart failure. European Journal of Heart Failure, 22(5), pp. 821-833. (doi: 10.1002/ejhf.1811) (PMID:32243695)

Abstract

Aims Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non‐ischaemic HF, it is important to better understand differences in underlying molecular mechanisms. Methods and results We performed a biological physical protein–protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT‐CHF study, 715 of whom had ischaemic HF and 445 had non‐ischaemic HF. Second, we constructed an enriched physical protein–protein interaction network, followed by a pathway over‐representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non‐ischaemic HF patients. We found 21/92 proteins to be up‐regulated and 2/92 down‐regulated in ischaemic relative to non‐ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin‐like growth factor binding protein‐1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort. Conclusions Pathophysiological pathways distinguishing patients with ischaemic HF from those with non‐ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF.

• Item Type: Articles
• Additional Information: This work was supported by a grant from the European Commission (FP7‐242209‐BIOSTAT-CHF).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Sama, I. E., Woolley, R. J., Nauta, J. F., Romaine, S. P.R., Tromp, J., ter Maaten, J. M., van der Meer, P., Lam, C. S.P., Samani, N. J., Ng, L. L., Metra, M., Dickstein, K., Anker, S. D., Zannad, F., Lang, C. C., Cleland, J. G.F., van Veldhuisen, D. J., Hillege, H. L., and oors, A. A.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 03 April 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in European Journal of Heart Failure 22(5):821-833
• Publisher Policy: Reproduced under a Creative Commons Licence