Altered mRNA Expression of Interleukin-1 Receptors in Myocardial Tissue of Patients with Left Ventricular Assist Device Support

Abstract

Serum levels of cytokines interleukin 1 beta (IL-1β) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue specimens of end-stage heart failure (HF) patients without (n = 24) and with MCS (n = 39; 594 ± 57 days) were analyzed for cytokine mRNA expression level of IL-1B, interleukin 1 receptor 1/2 (IL-1R1/2), interleukin 1 receptor-like 1 (IL-1RL1), IL-33 and interleukin-1 receptor accessory protein (IL-1RaP). MCS patients showed significantly elevated IL-1B expression levels (LV: 2.0 fold, p = 0.0058; RV: 3.3 fold, p < 0.0001). Moreover, IL-1R1, IL-1RaP and IL-33 expression levels strongly correlated with each other. IL-1RL1 and IL-1R2 expression levels were significantly higher in RV myocardial tissue (RV/LV ratio IL-1R2 HF: 4.400 ± 1.359; MCS: 4.657 ± 0.655; IL-1RL1 HF: 3.697 ± 0.876; MCS: 4.529 ± 0.5839). In addition, IL1-RaP and IL-33 RV expression levels were significantly elevated in MCS. Furthermore, IL-33 expression correlates with C-reactive protein (CRP) plasma levels in HF, but not in MCS patients. Increased expression of IL-1B and altered correlation patterns of IL-1 receptors indicate enhanced IL-1β signaling in MCS patients. Correlation of IL-1 receptor expression with IL-33 may hint towards a link between both pathways. Moreover, diverging expression in LV and RV suggests specific regulation of local cytokine signaling.

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“… 55 Interleukin-1 receptor accessory protein (IL1RAP) was elevated in LVRR- patients. According to Niazy et al, 56 plasma and myocardial levels of IL-1 and its receptors increase in heart failure and remain increased upon implantation of MCS devices.…”

Combining WGCNA and machine learning to identify mechanisms and biomarkers of ischemic heart failure development after acute myocardial infarction

“…In the serum of patients with heart failure, IL1B levels are highly abnormal and remain elevated after mechanical circulatory support. This indicates that IL1B elevation may run through the entire process of the development of IHF after AMI [ 40 ]. Targeting IL1B therapy has also achieved good results in animal experiments.…”

Myocardial Remodeling with Ventricular Assist Devices

“…Interleukins (IL) are a group of small molecules and peptides secreted by a wide variety of body cells or cytokines that function in cellular signaling and communication. Serum levels of members of IL-1 family cytokines, IL-1β and IL-33, are highly elevated in HF and remained elevated after MCS [54]. Increased expression of IL-1β and correlated patterns of IL-1 receptors indicate enhanced IL-1β signaling in MCS patients, while expression of IL-33 correlates with CRP plasma levels in HF, but not in patients on MCS.…”