A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure. - Université de Lorraine Accéder directement au contenu
Article Dans Une Revue European Journal of Heart Failure Année : 2020

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

Nilesh J Samani
  • Fonction : Auteur
  • PersonId : 869571

Résumé

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.
Fichier principal
Vignette du fichier
ejhf.1811.pdf (4.86 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03021520 , version 1 (24-11-2020)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Iziah E Sama, Rebecca J Woolley, Jan F Nauta, Simon P R Romaine, Jasper Tromp, et al.. A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure.. European Journal of Heart Failure, 2020, 22 (5), pp.821-833. ⟨10.1002/ejhf.1811⟩. ⟨hal-03021520⟩
30 Consultations
63 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More