Cell Reports Medicine (Sep 2024)
Clinical-transcriptional prioritization of the circulating proteome in human heart failure
- Andrew S. Perry,
- Kaushik Amancherla,
- Xiaoning Huang,
- Michelle L. Lance,
- Eric Farber-Eger,
- Priya Gajjar,
- Junedh Amrute,
- Lindsey Stolze,
- Shilin Zhao,
- Quanhu Sheng,
- Cassandra M. Joynes,
- Zhongsheng Peng,
- Toshiko Tanaka,
- Stavros G. Drakos,
- Kory J. Lavine,
- Craig Selzman,
- Joseph R. Visker,
- Thirupura S. Shankar,
- Luigi Ferrucci,
- Saumya Das,
- Jane Wilcox,
- Ravi B. Patel,
- Ravi Kalhan,
- Sanjiv J. Shah,
- Keenan A. Walker,
- Quinn Wells,
- Nathan Tucker,
- Matthew Nayor,
- Ravi V. Shah,
- Sadiya S. Khan
Affiliations
- Andrew S. Perry
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Kaushik Amancherla
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Xiaoning Huang
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Michelle L. Lance
- Masonic Medical Research Institute, Utica, NY, USA
- Eric Farber-Eger
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Priya Gajjar
- Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- Junedh Amrute
- Cardiology Division, Washington University School of Medicine, St. Louis, MO, USA
- Lindsey Stolze
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Shilin Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Quanhu Sheng
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
- Cassandra M. Joynes
- Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA
- Zhongsheng Peng
- Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA
- Toshiko Tanaka
- Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA
- Stavros G. Drakos
- Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA
- Kory J. Lavine
- Cardiology Division, Washington University School of Medicine, St. Louis, MO, USA
- Craig Selzman
- 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
- Joseph R. Visker
- Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA
- Thirupura S. Shankar
- Division of Cardiovascular Medicine, University of Utah and Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), Salt Lake City, UT, USA
- Luigi Ferrucci
- Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA
- Saumya Das
- Cardiovascular Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Jane Wilcox
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Ravi B. Patel
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Ravi Kalhan
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Sanjiv J. Shah
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Keenan A. Walker
- Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA
- Quinn Wells
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Nathan Tucker
- Masonic Medical Research Institute, Utica, NY, USA
- Matthew Nayor
- Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- Ravi V. Shah
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA; Corresponding author
- Sadiya S. Khan
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Corresponding author
- Journal volume & issue
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Vol. 5,
no. 9
p. 101704
Abstract
Summary: 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.
