Non-ischemic heart failure patients showed increased circulating monocyte frequencies and elevated CD4⁺ effector T-cells, but no increased myocardial immune cell infiltration.
Does non-ischemic heart failure alter the composition and effector functions of circulating and myocardial immune cells compared to controls?
Non-ischemic heart failure is associated with systemic immune activation and immunosenescence in peripheral blood, but this does not translate to increased immune cell infiltration in the myocardium.
Tasa de eventos absoluta: 0% vs 0%
Abstract Background Heart failure (HF) is characterized by systemic inflammation and adverse myocardial remodeling involving immune cell activation. Despite the recognized contribution of immune dysregulation to HF pathophysiology, effective immunomodulatory therapies remain lacking. Purpose This study aimed to characterize the composition and effector functions of circulating immune cells in patients with non-ischemic HF, and to determine whether systemic immune alterations are reflected in myocardial immune cell infiltration. Methods Peripheral blood mononuclear cells were isolated from patients with non-ischemic HF (n=19) and sex-matched controls without HF (n=19). Multiparametric flow cytometry was used to characterize monocyte subsets, dendritic cells (DCs), and T-cell subsets, as well as expression of pattern recognition receptors and immune checkpoint molecules. Monocyte effector function was assessed via intracellular cytokine staining following lipopolysaccharide (LPS) stimulation. Myocardial tissue from a subset of HF patients (n=7) and healthy controls (n=4) was analyzed for immune cell infiltration using immunohistochemistry (CD3, CD68, CD123 staining). Results HF patients exhibited increased circulating monocyte frequencies, with a relative reduction in non-classical (CD14⁻CD16⁺) monocytes. Monocytes displayed elevated PD-L1 expression, and intermediate/non-classical subsets had increased TLR4 levels. Cytokine production (IL-1β, IL-6, TNF-α) after LPS stimulation was unchanged. Reduced non-classical monocyte frequencies were associated with lower left ventricular ejection fraction, but not NT-proBNP levels. Circulating DCs were elevated. T-cell profiling revealed increased CD4⁺ effector Th and IL-17-producing (Th17) cells, alongside reduced regulatory T-cell frequencies. Despite systemic immune alterations, myocardial analysis showed no increased infiltration of T-cells, monocytes, or DCs in end-stage HF tissue compared to controls. Conclusion Non-ischemic end-stage HF is associated with systemic immune remodeling characterized by chronic activation and immunosenescence. However, these systemic changes are not paralleled by increased immune cell infiltration within myocardial tissue.For image description, please refer to the figure legend and surrounding text.
Baumhove et al. (Sun,) reported a other. Non-ischemic heart failure patients showed increased circulating monocyte frequencies and elevated CD4⁺ effector T-cells, but no increased myocardial immune cell infiltration.