Clinical-transcriptional prioritization of the circulating proteome in human heart failure.

Autor:	Perry AS; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Amancherla K; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Huang X; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Lance ML; Masonic Medical Research Institute, Utica, NY, USA., Farber-Eger E; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Gajjar P; Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Amrute J; Cardiology Division, Washington University School of Medicine, St. Louis, MO, USA., Stolze L; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Zhao S; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Sheng Q; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Joynes CM; Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA., Peng Z; Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA., Tanaka T; Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA., Drakos SG; Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA., Lavine KJ; Cardiology Division, Washington University School of Medicine, St. Louis, MO, USA., Selzman C; Department of Cardiac Surgery, University of Utah School of Medicine, Division of Cardiothoracic Surgery, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA., Visker JR; Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA., Shankar TS; Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA., Ferrucci L; Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA., Das S; Cardiovascular Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Wilcox J; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Patel RB; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Kalhan R; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Shah SJ; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Walker KA; Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA., Wells Q; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Tucker N; Masonic Medical Research Institute, Utica, NY, USA., Nayor M; Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Shah RV; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: ravi.shah@vumc.org., Khan SS; Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: s-khan-1@northwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Sep 17; Vol. 5 (9), pp. 101704. Date of Electronic Publication: 2024 Sep 02.
DOI:	10.1016/j.xcrm.2024.101704
Abstrakt:	Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation. Competing Interests: Declaration of interests S.G.D. is a consultant for Abbott, and S.G.D. and K.J.L. have industry research support from Novartis. R.V.S. has served as a consultant for Amgen, Cytokinetics, and Thryv Therapeutics (with options ownership in Thryv). R.V.S. is a co-inventor on a patent for ex-RNA signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. R.V.S. also has stock options with Thryv Therapeutics. A.S.P. is a co-inventor on a pending patent for proteomic signatures of fitness, lung, and liver diseases. K.A. does ad hoc consulting for Tegus and Guidepoint and serves on a DSMB for Fortrea. M.N. has received speaking honoraria from Cytokinetics. K.J.L. serves as a consultant for Medtronic, Implicit Biosciences, Kiniksa Pharmaceuticals, and Cytokinetics. K.J.L. receives grant support from Amgen, Novartis, Kiniksa Pharmaceuticals, and Implicit Biosciences. S.D. is a co-founder and has equity in Thryv therapeutics and Switch Therapeutics. S.D. has received grant support from Abbot Laboratories and Bristol Myers Squib. S.D. is a co-inventor on a patent on tissue-specific EV-RNAs. R.K. has received personal fees from GSK, Astrazeneca, Boehringer Ingelheim, and CVS Caremark. S.J.S. has received consulting fees from 35Pharma, Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, BaroPace, Bayer, Boehringer-Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, eMyosound, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, SalubriusBio, Sardocor, Shifamed, Tectonic, Tenax, Tenaya, Ulink, and Ultromics. J.M.A. was employed by Amgen. J.W. reports consulting/scientific advisory board for Abiomed, Abbott, Astra Zeneca, Boehringer Ingelheim, and Cytokinetics within the last 24 months. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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