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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)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Heart Failure ; Hypertension ; Inflammation ; Microcirculation ; Stroke Volume; Perivascular Adipose-tissue; Nitro-fatty Acids; Heart-failure; Inflammation
ISSN (print) / ISBN 0009-7330
e-ISSN 1524-4571
Journal Circulation Research
Quellenangaben Volume: 137, Issue: 5, Pages: 682-698 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants German Research Foundation (Deutsche Forschungsgemeinschaft