Crucial Role of Interleukin-6 in the Development of Norepinephrine-induced Left Ventricular Remodeling in Mice

Abstract

Background: Elevated serum concentration of interleukin (IL)-6 is a predictor for poor prognosis in congestive heart failure. It was shown previously in rats, that IL-6 expression in the left ventricle (LV) was followed by LV hypertrophy. Methods: Using IL-6 deficient mice (IL-6^-/-), we studied the role of IL-6 in a model of norepinephrine (NE)-induced LV hypertrophy. Results: In wild type (WT) mice, IL-6 mRNA expression and its concentration in the serum were elevated after 4 h of NE-treatment (s.c. 0.25 mg/kg·h). Further, NE-induced LV hypertrophy was detected: LV weight/body weight (LVW/BW) ratio (+12.3±3%, p < 0.05) and mRNA expression of atrial natriuretic peptide (ANP) in WT mice (+120±25%, p < 0.05) after 3 days were increased. In contrast, NE did not induce elevation of LVW/BW ratio and ANP expression in IL-6^-/- mice. Replacement with recombinant IL-6 restored the hypertrophy-inducing effect of NE in IL-6^-/- mice. As to the extracellular matrix (ECM) proteins, NE increased collagen type I and III expression only in WT mice and not in IL-6^-/- mice. The addition of recombinant IL-6 elevated the expression of the ECM proteins to the WT level. Conclusion: IL-6 is a major player in the development of NE-induced LV hypertrophy in mice.

α1A-Adrenergic Receptors Regulate Cardiac Hypertrophy In Vivo Through Interleukin-6 Secretion

“…7A). In addition, norepinephrine failed to initiate hypertrophy in IL-6 KO mice (Meier et al, 2009) and IL-6 failed to initiate a hypertrophic response in a 1A/B KO mice (Fig. 7C), suggesting that IL-6 is a prominent factor in a 1 -AR-mediated cardiac hypertrophy.…”

Cardiac Tissue-Restricted Deletion of Plakoglobin Results in Progressive Cardiomyopathy and Activation of β-Catenin Signaling

“…Furthermore, it has been reported that the serum concentration of IL-6 increases after myocardial infarction, congestive heart failure, and hypertrophic and dilated cardiomyopathy (14). IL-6 can promote myocyte hypertrophy and induce norepinephrine-mediated LV remodeling (32). IL-6/gp130-mediated signaling is involved in overload-induced cardiac hypertrophy in the rodent heart (35).…”

Low Circulating Levels of Mitochondrial and High Levels of Nuclear DNA Predict Mortality in Chronic Heart Failure

“…Among other inflammatory cytokines that have been studied in animals is IL-6, which has been shown to induce negative inotropic effects (82,83,84) as well as hypertrophy, fibrosis, and diastolic dysfunction (85). IL-1β is a cytokine in the IL-1 family that has gained growing attention as previous clinical studies have shown a significant beneficial effect by inhibiting IL-1β (55,86,87).…”