Clinical-transcriptional prioritization of the circulating proteome in human heart failure
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.
Authors
- Andrew Perry (ORCID: https://orcid.org/0000-0003-3342-6158)
- Junedh Amrute (ORCID: https://orcid.org/0000-0002-6851-0168)
- Joseph R. Visker (ORCID: https://orcid.org/0000-0002-8490-6111)
- Kory J. Lavine (ORCID: https://orcid.org/0000-0003-1948-9945)
- Lindsey K. Stolze (ORCID: https://orcid.org/0000-0003-2269-769X)
- Kaushik V Amancherla (ORCID: https://orcid.org/0000-0003-3379-5834)
- Ravi V. Shah (ORCID: https://orcid.org/0000-0002-4471-7156)
- Zhongsheng Peng (ORCID: https://orcid.org/0000-0001-7000-8647)
- Saumya Das (ORCID: https://orcid.org/0000-0002-4521-4606)
- Jane E. Wilcox (ORCID: https://orcid.org/0000-0002-9272-7623)
- Eric Farber‐Eger (ORCID: https://orcid.org/0000-0003-0281-3796)
- Matthew Nayor (ORCID: https://orcid.org/0000-0002-6993-9396)
- Ravi Kalhan (ORCID: https://orcid.org/0000-0003-2443-0876)
- Quanhu Sheng (ORCID: https://orcid.org/0000-0001-8951-9295)
- Craig Selzman
- Luigi Ferrucci (ORCID: https://orcid.org/0000-0002-6273-1613)
- Xiaoning Huang (ORCID: https://orcid.org/0000-0002-5858-6281)
- Quinn S. Wells (ORCID: https://orcid.org/0000-0003-3899-0313)
- Nathan R. Tucker (ORCID: https://orcid.org/0000-0002-5071-4218)
- Stavros G. Drakos (ORCID: https://orcid.org/0000-0002-1223-327X)
- Priya Gajjar
- Keenan A. Walker (ORCID: https://orcid.org/0000-0002-5989-9853)
- Ravi B. Patel (ORCID: https://orcid.org/0000-0002-8328-746X)
- Toshiko Tanaka (ORCID: https://orcid.org/0000-0002-4161-3829)
- Sadiya S. Khan (ORCID: https://orcid.org/0000-0003-0643-1859)
- Thirupura S. Shankar (ORCID: https://orcid.org/0000-0002-5009-2770)
- Shilin Zhao (ORCID: https://orcid.org/0000-0002-3787-8111)
- Sanjiv J. Shah (ORCID: https://orcid.org/0000-0002-5655-8201)
- Cassandra M Joynes
- Michelle L Lance (ORCID: https://orcid.org/0000-0001-7607-9315)
Institutions
- Boston University (US)
- Northwestern University (US)
- Harvard University (US)
- Vanderbilt University (US)
- Washington University in St. Louis (US)
- University of Utah (US)
- Massachusetts General Hospital (US)
- Masonic Medical Research Laboratory (US)
- National Institute on Aging (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101704
- Citations
- 7
- Primary Topic
- Cardiac Fibrosis and Remodeling
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- U.S. Department of Veterans Affairs
- Bill and Melinda Gates Foundation
- American Heart Association
- Pfizer
- AstraZeneca
- Northwestern University
- University of Minnesota
- Boston Scientific Corporation
- Children's Discovery Institute
- Nora Eccles Treadwell Foundation
- Fondation Leducq
- National Institutes of Health
- Kaiser Foundation Research Institute
- National Institute on Aging
- National Heart, Lung, and Blood Institute