Proteomic Signatures During Treatment in Different Stages of Heart Failure.

Autor:	Michelhaugh SA; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.)., Camacho A; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.)., Ibrahim NE; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.).; Harvard Medical School, Boston, MA (N.E.I., H.G., E.G., G.D.L., J.L.J.)., Gaggin H; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.).; Harvard Medical School, Boston, MA (N.E.I., H.G., E.G., G.D.L., J.L.J.)., D'Alessandro D; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.)., Coglianese E; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.).; Harvard Medical School, Boston, MA (N.E.I., H.G., E.G., G.D.L., J.L.J.)., Lewis GD; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.).; Harvard Medical School, Boston, MA (N.E.I., H.G., E.G., G.D.L., J.L.J.)., Januzzi JL Jr; Massachusetts General Hospital, Boston (S.A.M., A.C., N.E.I., H.G., D.D., E.C., G.D.L., J.L.J.).; Harvard Medical School, Boston, MA (N.E.I., H.G., E.G., G.D.L., J.L.J.).; Baim Institute for Clinical Research, Boston, MA (J.L.J.).
Jazyk:	angličtina
Zdroj:	Circulation. Heart failure [Circ Heart Fail] 2020 Aug; Vol. 13 (8), pp. e006794. Date of Electronic Publication: 2020 Jul 29.
DOI:	10.1161/CIRCHEARTFAILURE.119.006794
Abstrakt:	Background: Proteomics have already provided novel insights into the pathophysiology of heart failure (HF) with reduced ejection fraction. Previous studies have evaluated cross-sectional protein signatures of HF, but few have characterized proteomic changes following HF with reduced ejection fraction treatment with ARNI (angiotensin receptor/neprilysin inhibitor) therapy or left ventricular assist devices. Methods: In this retrospective omics study, we performed targeted proteomics (N=625) of whole blood sera from patients with American College of Cardiology/American Heart Association stage D (N=29) and stage C (N=12) HF using proximity extension assays. Samples were obtained before and after (median=82 days) left ventricular assist device implantation (stage D; primary analysis) and ARNI therapy initiation (stage C; matched reference). Oblique principal component analysis and point biserial correlations were used for feature extraction and selection; standardized mean differences were used to assess within and between-group differences; and enrichment analysis was used to generate and cluster Gene Ontology terms. Results: Core sets of proteins were identified for stage C (N=9 proteins) and stage D (N=18) HF; additionally, a core set of 5 shared HF proteins (NT-proBNP [N-terminal pro-B type natriuretic peptide], ESM [endothelial cell-specific molecule]-1, cathepsin L1, osteopontin, and MCSF-1) was also identified. For patients with stage D HF, moderate (δ, 0.40-0.60) and moderate-to-large (δ, 0.60-0.80) sized differences were observed in 8 of their 18 core proteins after left ventricular assist devices implantation. Additionally, specific protein groups reached concentration levels equivalent ( g <0.10) to stage C HF after initiation on ARNI therapy. Conclusions: HF with reduced ejection fraction severity associates with distinct proteomic signatures that reflect underlying disease attributes; these core signatures may be useful for monitoring changes in cardiac function following initiation on ARNI or left ventricular assist device implantation.
Databáze:	MEDLINE
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