Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

Amil M. Shah (), Peder L. Myhre, Victoria Arthur, Pranav Dorbala, Humaira Rasheed, Leo F. Buckley, Brian Claggett, Guning Liu, Jianzhong Ma, Ngoc Quynh Nguyen, Kunihiro Matsushita, Chiadi Ndumele, Adrienne Tin, Kristian Hveem, Christian Jonasson, Håvard Dalen, Eric Boerwinkle, Ron C. Hoogeveen, Christie Ballantyne, Josef Coresh, Torbjørn Omland and Bing Yu
Additional contact information
Amil M. Shah: University of Texas Southwestern Medical Center
Peder L. Myhre: Akershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo
Victoria Arthur: University of Texas Southwestern Medical Center
Pranav Dorbala: Brigham and Women’s Hospital
Humaira Rasheed: Akershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo
Leo F. Buckley: Brigham and Women’s Hospital
Brian Claggett: Brigham and Women’s Hospital
Guning Liu: University of Texas Health Sciences Center at Houston
Jianzhong Ma: University of Texas Health Sciences Center at Houston
Ngoc Quynh Nguyen: University of Texas Health Sciences Center at Houston
Kunihiro Matsushita: Johns Hopkins Bloomberg School of Public Health
Chiadi Ndumele: Johns Hopkins Bloomberg School of Public Health
Adrienne Tin: University of Mississippi Medical Center
Kristian Hveem: Norwegian University of Science and Technology
Christian Jonasson: Norwegian University of Science and Technology
Håvard Dalen: Norwegian University of Science and Technology
Eric Boerwinkle: University of Texas Health Sciences Center at Houston
Ron C. Hoogeveen: Baylor College of Medicine
Christie Ballantyne: Baylor College of Medicine
Josef Coresh: NYU Langone Health
Torbjørn Omland: Akershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo
Bing Yu: University of Texas Health Sciences Center at Houston

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

Date: 2024
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DOI: 10.1038/s41467-023-44680-3

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