Faculty, Staff and Student Publications
Publication Date
1-15-2024
Journal
Nature Communications
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.
Keywords
Humans, Proteomics, Heart Failure, Risk Factors, Atherosclerosis, Phenotype, Carrier Proteins, Glycoproteins, Extracellular Matrix Proteins
DOI
10.1038/s41467-023-44680-3
PMID
38225249
PMCID
PMC10789789
PubMedCentral® Posted Date
1-15-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes