Kneuer, J.M.* ; Müller, M.* ; Erbe, S.* ; Kokot, K.E.* ; Rosch, S.* ; Müller-Kozarez, I.* ; Schrö, S.C.* ; Maeder, C.* ; Heitkamp, S.F.* ; Gaul, S.* ; von Haehling, S.* ; Tönjes, A.* ; Blüher, M. ; Lurz, P.* ; Wachter, R.* ; Klinke, A.* ; Laufs, U.* ; Boeckel, J.N.*
Circulating immune cell signature analysis in HFpEF across species.
Circ. Res. 137, 682-698 (2025)
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical picture that is closely related to extracardiac comorbidities such as obesity, hypertension, and diabetes and is associated with chronic, low-grade systemic inflammation. Previous studies on myocardial biopsies of patients with HFpEF showed intramyocardial inflammatory activity, suggesting that the inflammatory processes in HFpEF are predominantly systemic and exhibit compartment-specific patterns. METHODS: We performed single-cell RNA sequencing of peripheral blood mononuclear cells of patients with HFpEF (n=6), heart failure with reduced ejection fraction patients (n=8), and healthy controls (n=7), taking obesity status into account. For validation, bulk RNA sequencing was performed on whole blood samples. In parallel, the systemic immune cell response was investigated in an HFpEF mouse model (induced by a high-fat diet plus L-NAME), with one group additionally administered the anti-inflammatory agent nitro-oleic acid. RESULTS: Analysis of human peripheral blood mononuclear cells revealed an HFpEF-specific inflammatory fingerprint, which manifested in obesity-related increased expression of cytokine signaling genes (eg, CCL2 and TNF) and obesity-independent increases in mitochondrial-associated activity. In the mouse model, HFpEF animals showed a comparable increase in inflammatory markers, with treatment with nitro-oleic acid leading to a partial normalization of immunologic signatures and a significant improvement in diastolic function. CONCLUSIONS: Our results demonstrate that the immune cells of patients with HFpEF are characterized by a distinct transcriptional immune signature that differs from that of patients with heart failure with reduced ejection fraction analyzed in this study. The conserved immunologic signatures between the human and murine data sets analyzed here, and the beneficial effect of nitro-oleic acid in the preclinical model induced by high-fat diet and L-NAME, provide translational insights and generate hypotheses for personalized interventions in HFpEF.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Heart Failure ; Hypertension ; Inflammation ; Microcirculation ; Stroke Volume; Perivascular Adipose-tissue; Nitro-fatty Acids; Heart-failure; Inflammation
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2025
Prepublished im Jahr
0
HGF-Berichtsjahr
2025
ISSN (print) / ISBN
0009-7330
e-ISSN
1524-4571
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 137,
Heft: 5,
Seiten: 682-698
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Lippincott Williams & Wilkins
Verlagsort
Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-506501-001
Förderungen
German Research Foundation (Deutsche Forschungsgemeinschaft
Copyright
Erfassungsdatum
2025-07-28