Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction

Elise L Kessler; Elisa Dal Canto; Ernest Diez-Benavente; Anne-Mar van Ommen; Daniek Kapteijn; Marleen C Glade; Siroon Bekkering; Saskia Haitjema; Gideon Valstar; Maarten J Cramer; Frans H Rutten; Arco J Teske; Roxana Menken; Leonard Hofstra; Hester M den Ruijter; Niels P Riksen; Saskia C A de Jager

doi:10.1016/j.ijcard.2025.133161

Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction

Elise L Kessler, Elisa Dal Canto, Ernest Diez-Benavente, Anne-Mar van Ommen, Daniek Kapteijn, Marleen C Glade, Siroon Bekkering, Saskia Haitjema, Gideon Valstar, Maarten J Cramer, Frans H Rutten, Arco J Teske, Roxana Menken, Leonard Hofstra, Hester M den Ruijter, Niels P Riksen, Saskia C A de Jager^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).

OBJECTIVE: To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF.

METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD.

RESULTS: Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041).

CONCLUSIONS: LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.

Original language	English
Article number	133161
Number of pages	9
Journal	International Journal of Cardiology
Volume	429
Early online date	13 Mar 2025
DOIs	https://doi.org/10.1016/j.ijcard.2025.133161
Publication status	Published - 15 Jun 2025

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Kessler, E. L., Dal Canto, E., Diez-Benavente, E., van Ommen, A.-M., Kapteijn, D., Glade, M. C., Bekkering, S., Haitjema, S., Valstar, G., Cramer, M. J., Rutten, F. H., Teske, A. J., Menken, R., Hofstra, L., den Ruijter, H. M., Riksen, N. P., & de Jager, S. C. A. (2025). Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. International Journal of Cardiology, 429, Article 133161. https://doi.org/10.1016/j.ijcard.2025.133161

@article{be8cd0c2715046d38f45c29ede356c71,

title = "Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction",

abstract = "BACKGROUND: Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).OBJECTIVE: To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF.METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD.RESULTS: Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041).CONCLUSIONS: LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.",

author = "Kessler, {Elise L} and {Dal Canto}, Elisa and Ernest Diez-Benavente and {van Ommen}, Anne-Mar and Daniek Kapteijn and Glade, {Marleen C} and Siroon Bekkering and Saskia Haitjema and Gideon Valstar and Cramer, {Maarten J} and Rutten, {Frans H} and Teske, {Arco J} and Roxana Menken and Leonard Hofstra and {den Ruijter}, {Hester M} and Riksen, {Niels P} and {de Jager}, {Saskia C A}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = jun,

day = "15",

doi = "10.1016/j.ijcard.2025.133161",

language = "English",

volume = "429",

journal = "International Journal of Cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

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Kessler, EL, Dal Canto, E, Diez-Benavente, E, van Ommen, A-M, Kapteijn, D, Glade, MC, Bekkering, S, Haitjema, S, Valstar, G, Cramer, MJ, Rutten, FH, Teske, AJ, Menken, R, Hofstra, L, den Ruijter, HM, Riksen, NP & de Jager, SCA 2025, 'Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction', International Journal of Cardiology, vol. 429, 133161. https://doi.org/10.1016/j.ijcard.2025.133161

Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. / Kessler, Elise L; Dal Canto, Elisa; Diez-Benavente, Ernest et al.
In: International Journal of Cardiology, Vol. 429, 133161, 15.06.2025.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction

AU - Kessler, Elise L

AU - Dal Canto, Elisa

AU - Diez-Benavente, Ernest

AU - van Ommen, Anne-Mar

AU - Kapteijn, Daniek

AU - Glade, Marleen C

AU - Bekkering, Siroon

AU - Haitjema, Saskia

AU - Valstar, Gideon

AU - Cramer, Maarten J

AU - Rutten, Frans H

AU - Teske, Arco J

AU - Menken, Roxana

AU - Hofstra, Leonard

AU - den Ruijter, Hester M

AU - Riksen, Niels P

AU - de Jager, Saskia C A

PY - 2025/6/15

Y1 - 2025/6/15

N2 - BACKGROUND: Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).OBJECTIVE: To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF.METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD.RESULTS: Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041).CONCLUSIONS: LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.

AB - BACKGROUND: Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).OBJECTIVE: To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF.METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD.RESULTS: Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041).CONCLUSIONS: LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.

U2 - 10.1016/j.ijcard.2025.133161

DO - 10.1016/j.ijcard.2025.133161

M3 - Article

C2 - 40088950

SN - 0167-5273

VL - 429

JO - International Journal of Cardiology

JF - International Journal of Cardiology

M1 - 133161

ER -

Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction

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