Faculty, Staff and Student Publications
Publication Date
11-20-2023
Journal
Nature Communications
Abstract
Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.
Keywords
Humans, Heart Failure, Stroke Volume, Dyspnea, Exercise Test, Eicosanoids, Exercise Tolerance, Heart failure, Molecular medicine, Inflammation
DOI
10.1038/s41467-023-43363-3
PMID
37985769
PMCID
PMC10662264
PubMedCentral® Posted Date
11-20-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes