Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy

Abstract

Objective: To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression. Methods: Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor a (TNFa), interleukin (IL) -1b, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM. Results: Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p , 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p , 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm 2 , p , 0.001). Upregulation of TNFa, IL-1b, and IL-6 gene expression was detected in both groups. However, TNFa gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFa gene expression. In patients with AS there was a strong inverse relation between circulating TNFa and TNFa gene expression (r = 20.685, p = 0.014), between circulating TNFa and IL-1b gene expression (r = 20.664, p = 0.018), and between soluble TNF receptor 2 and TNFa gene expression (r = 20.685, p = 0.020). Myocardial gene expression of TNFa was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFa gene expression than were patients with well compensated DCM (p = 0.011). Conclusion: TNFa gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFa gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.

Delta-6-desaturase Links Polyunsaturated Fatty Acid Metabolism With Phospholipid Remodeling and Disease Progression in Heart Failure

“…This is consistent with clinical evidence for a greater degree of inflammation associated with compensatory hypertrophy during early aortic stenosis when compared with decompensated HF groups. 38 Therefore, NFκB may mediate temporal and model-specific effects that are differentially modulated by altered myocardial eicosanoid levels and membrane PUFA composition.…”

Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A

“…Experimental induction of hemodynamic overload in the adult mammalian heart has been shown to provoke a transient increase in pro-inflammatory cytokines (2). Furthermore, cardiac-specific over expression of IL-6 and TNF-α in mice hearts has been shown to develop cardiac hypertrophy and ventricular dysfunction similar to that seen in human disease conditions, suggesting that cytokines are critically involved in the cardiac remodeling process (9,30).…”

“…The aforementioned cytokines play a dual role, activating apoptosis in myocytes (13), while also functioning in a cytoprotective manner (15). Furthermore, inappropriate activation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) have been recognized as an important mediator in the development of endothelial dysfunction, cardiac hypertrophy, and heart failure in experimental animal models and in humans (9,17,28,30). Atrial natriuretic peptide (ANP) has been shown to inhibit the TNF-α induced adhesion molecule expression in endothelial cells (32).…”

Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice

“…Several lines of evidence indicate that the activation of hypertrophic markers, matrix metalloproteinases (MMPs), and proinflammatory cytokines play a central pathophysiological roles in the development of cardiac hypertrophy, fibrosis, and heart failure in the experimental animal models and humans (11,52,58,66). Previous studies have suggested that ANP/ NPRA signaling acts as a negative regulator of inflammation and hypertrophic growth (14,65,67,69).…”