The immunophenotype of peripheral blood monocytes in aortic stenosis during different rates of disease progression

Abstract

Aortic stenosis (AS) is a common valvular heart disease (Iung et al., 2019) with an increasing prevalence (Danielsen et al., 2014) and potentially fatal consequences (Members et al., 2012). Currently, treatment is mainly limited to surgical or interventional aortic valve replacement (Otto et al., 2021b). Disease progression varies significantly between patients, and predicting its course remains challenging (Willner et al., 2023), partly due to an incomplete understanding of the underlying pathophysiology. Recent research has shifted away from the theory of passive development toward an active process heavily influenced by various immune cells (Goody et al., 2020b, Bartoli-Leonard et al., 2021). Monocytes are gaining growing interest due to their influence on disease initiation and progression (Lassalle et al., 2022, Zhang et al., 2022b). The aim of this study was to gain deeper insights into the influence of monocytes on the progression rate of AS. Patients with severe symptomatic aortic stenosis were divided into two groups based on the annualized change in maximum transvalvular flow velocity measured during echocardiography: (1) fast progressive AS (FP-AS) and (2) slow progressive AS (SP-AS). Peripheral blood monocytes from both patient groups were analysed using flow cytometry, including both traditional and unsupervised analytical approaches. A comparison of the monocyte immunophenotypes revealed significant differences between patients with fast AS progression and those with slow AS progression. Monocytes from FP-AS patients exhibited an elevated expression of various chemokines and receptors, which may contribute to an accelerated disease progression through their distinct functions. Most striking was the upregulated expression of the chemokine MIF, which is already known for its pro-inflammatory effects in several diseases (Calandra and Roger, 2003, Bernhagen et al., 2007). Further analyses by Mueller et al. (2024) of the same patient cohort support the pro-inflammatory influence of MIF and its interaction with immune cells in FP-AS. These findings collectively suggest a critical role for monocytes and MIF in the pathophysiology of FP-AS. Consequently, alteration of monocyte activity and Inhibition of MIF may represent promising therapeutic approaches for FP-AS and should be subject to future investigations. Furthermore, the identification of patients at risk of FP-AS might be facilitated in the future through analysis of chemokine expression profiles.