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Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure

Joao Pedro Ferreira 1, 2 Job Verdonschot 3, 4 Timothy Collier 5 Ping Wang 4 Anne Pizard 2, 1, 6 Christian Bär 7 Jens Björkman Alessandro Boccanelli Javed Butler 8, 9, 10 Andrew Clark 11 John Cleland 12, 13 Christian Delles 14 Javier Díez 15, 16, 17, 18 Nicolas Girerd 1, 2 Arantxa González 15, 16, 17, 18 Mark Hazebroek 3 Anne Huby 1, 2 Wouter Jukema 19 Roberto Latini 20 Joost Leenders Daniel Lévy 21, 22 Alexandre Mebazaa 23 Harald Mischak Florence Pinet 24 Patrick Rossignol 1, 2 Naveed Sattar 14 Peter Sever 25 Jan Staessen 26 Thomas Thum 27, 25 Nicolas Vodovar 23 Zhen-Yu Zhang 26 Stephane Heymans 3, 26 Faiez Zannad 1, 2
Abstract : Background Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies. Methods and Results To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin-angiotensin-aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis. Conclusions Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF. Clinical Trial Registration: URL: . Unique identifier: NCT02556450.
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Submitted on : Monday, August 19, 2019 - 11:34:35 AM
Last modification on : Wednesday, December 30, 2020 - 5:42:09 PM

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Joao Pedro Ferreira, Job Verdonschot, Timothy Collier, Ping Wang, Anne Pizard, et al.. Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure. Circulation. Heart failure, Lippincott Williams & Wilkins, 2019, 12 (5), pp.e005897. ⟨10.1161/CIRCHEARTFAILURE.118.005897⟩. ⟨hal-02267410⟩



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