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Updated: May 22, 2025
Murine Echocardiography of Left Atrium, Aorta, and Pulmonary Artery
Published on: February 20, 2017
Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart
Elise L Kessler1, Elisa Dal Canto2, Ernest Diez-Benavente3
1Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Utrecht Regenerative Medicine Center, Circulatory Health Laboratory, University, Utrecht, the Netherlands.
Insights
Inflammatory conditions like obesity and diabetes are linked to heart failure. This study found that specific monocyte subtypes are associated with left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Obesity and diabetes, characterized by inflammation, are linked to intermediate/non-classical monocyte activation.
- This monocyte activation contributes to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF).
Purpose of the Study:
- To investigate the association between circulating monocyte subtypes and their activity with LVDD and HFpEF.
- To explore the relationship between immunological markers and echocardiographic indicators of diastolic dysfunction.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF.
- Flow cytometry for monocyte subtype characterization and macrophage polarization assessment.
- Cytokine secretion measurement, RNA sequencing for gene expression, and correlation with echocardiographic data.
Main Results:
- LVDD patients showed significantly lower Interleukin-6 secretion compared to controls.
- HFpEF patients had increased intermediate and non-classical monocytes; LVDD/HFpEF macrophages showed a shift towards M2 polarization.
- Higher non-classical monocyte counts correlated with impaired diastolic function (lower E' septal velocity).
Conclusions:
- LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes.
- Increased non-classical monocytes correlate with diastolic impairment, highlighting inflammation's role in LVDD and HFpEF.
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.
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