Abstract
Background: Ghrelin may exert positive effects on cardiac structure and function in heart failure (HF) patients. Methods: We assessed ghrelin levels in 266 dilated cardiomyopathy (DCM) patients and in 200 age, gender and body mass index (BMI) matched controls. Further, we evaluated the expression of ghrelin and growth hormone secretagogue-receptor (GHSR) in the myocardium of 41 DCM patients and in 11 controls. Results: DCM patients had significantly lower levels of total, acylated and unacylated ghrelin when compared to controls (p < 0.05 for all). In controls, we observed a negative correlation of ghrelin with age, male gender and BMI. These correlations were lost in the DCM group, except for male gender. Total ghrelin was higher in patients with more recent diagnosis when compared to patients with longer duration of the DCM (p = 0.033). Further, total ghrelin was higher in patients with lower left ventricular systolic function (<40% LVEF, vs. 40% ≤ LVEF < 49% vs. LVEF ≥ 50%: 480.8, vs. 429.7, vs. 329.5 pg/mL, respectively, p = 0.05). Ghrelin prepropeptide was expressed more in DCM patients than in controls (p = 0.0293) while GHSR was expressed less in DCM patients (p < 0.001). Furthermore, ghrelin showed an inverse correlation with its receptor (ρ = −0.406, p = 0.009), and this receptor showed a significant inverse correlation with Interleukin-1β (ρ = −0.422, p = 0.0103). Conclusion: DCM duration and severity are accompanied by alterations in the ghrelin–GHSR system.
Highlights
Idiopathic dilated cardiomyopathy (DCM) is a progressive heart muscle disease, defined by the presence of left ventricular or biventricular dilatation and dysfunction [1], whose most common first manifestation is heart failure (HF)
In samples obtained from explanted, failing and normal hearts, we evaluated the expression of ghrelin prepropeptide, the ghrelin receptor growth hormone secretagogue-receptor (GHSR), and IL-1β
We thoroughly investigated, for the first time, the association between the levels of ghrelin, myocardial disease duration, left ventricular ejection fraction and NYHA class in a large cohort of patients with DCM and long-term follow-up
Summary
Idiopathic dilated cardiomyopathy (DCM) is a progressive heart muscle disease, defined by the presence of left ventricular or biventricular dilatation and dysfunction [1], whose most common first manifestation is heart failure (HF). Ghrelin is a gastric peptide, synthesized from a gene encoding for a prepropeptide that is subsequently cleaved to generate both ghrelin and obestatin These peptides exert opposite effects on food intake, where the first is orexigenic, while the second is anorexigenic [6]. In a DCM animal model, ghrelin administration significantly improved the life expectancy compared with controls [12]. Methods: We assessed ghrelin levels in 266 dilated cardiomyopathy (DCM) patients and in 200 age, gender and body mass index (BMI) matched controls. Results: DCM patients had significantly lower levels of total, acylated and unacylated ghrelin when compared to controls (p < 0.05 for all). Total ghrelin was higher in patients with lower left ventricular systolic function (
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