IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult

Abstract

Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.

Stimulation of β‐adrenoceptors up‐regulates cardiac expression of galectin‐3 and BIM through the Hippo signalling pathway

“…Collectively, these data suggest involvement of the AC/cAMP/PKA pathway in β‐adrenoceptor‐Mst1(Hippo) signalling that regulates expression of Gal‐3 and BIM. It is well recognized that chronic β‐adrenoceptor stimulation occurs in models of heart disease due to almost any aetiology leading to cardiac apoptosis and fibrosis (G. J. Lee, Yan, Vatner, & Vatner, ; Peter et al, ; Xiao et al, ; Xu et al, ). Our study provides the mechanistic link by showing the coupling of β‐adrenoceptors with the Hippo pathway as well as up‐regulated Gal‐3 and BIM as the target genes.…”

“…Data shown are means ± SEM and were compared by two-tailed Student's t test (a), two-way (b) or one-way (c) ANOVA, followed by Bonferroni post hoc test almost any aetiology leading to cardiac apoptosis and fibrosis (G. J. Lee, Yan, Vatner, & Vatner, 2015;Peter et al, 2007;Xiao et al, 2018;Xu et al, 2011). Our study provides the mechanistic link by showing the coupling of β-adrenoceptors with the Hippo pathway as well as up-regulated Gal-3 and BIM as the target genes.…”

“…However, in the setting of heart disease, sustained stimulation of β-adrenoceptors, due to enhanced sympathetic nervous activation with elevated catecholamine levels is associated with adverse prognosis (Cohn et al, 1984;Kaye et al, 1995). It is well known that sustained β-adrenoceptor stimulation leads to adverse cardiac effects notably fibrosis and cardiomyocyte apoptosis (Triposkiadis et al, 2009;Xiao et al, 2018). Understanding the mechanisms that drive myocardial fibrosis and apoptosis is essential for the development of new therapies.…”

Cardiac fibroblast‐specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin‐6 signaling mechanism

“…Although we did not identify the precise bioactive molecule(s) in the cardiac DAMP preparation responsible for p38a activation and IL-6 expression in cardiac fibroblasts, we did establish that those effects occurred independent of the IL-1R1 or TLR4 receptors. There are several other candidate molecules and receptors that could fulfill that role (20,40), including IL-18 (an IL-1 family cytokine that acts via a different receptor), which has recently been shown to be up-regulated in response to ISO treatment in mice, and its release from damaged cardiomyocytes triggered inflammation and pathologic cardiac remodeling (68). We also cannot rule out that combinations of molecules in the DAMP preparation were driving IL-6 secretion, rather than a single, specific molecule, especially given the diversity of molecules up-regulated in the remodeled heart that are known to induce IL-6 secretion from fibroblasts in a p38-dependent manner (1,48,49).…”

Noninvasive light emitting diode therapy: A novel approach for postinfarction ventricular arrhythmias and neuroimmune modulation

“…32,33 Moreover, in the first 3 to 12 hours after AMI, expression of IL-1β and IL-6 was significantly increased in both the infarct and noninfarcted myocardium. 31 Furthermore, previous studies 34 might reverse these changes. 34 In the present study, we also found that there was a significant increase in sympathetic neural activity and IL-18, IL-1β, and NGF expression in the first 3 hours after AMI.…”