Human heart shifts from IGF-1 production to utilization with chronic heart failure

Chronic heart failure (CHF) is characterized by multiple hormonal and metabolic deficiencies (MHD). In this context, abnormalities of growth hormone (GH) and its effector insulin like growth factor-1 (IGF-1) play a distinct and relevant role. Circulating levels of IGF-1 have been associated with cardiovascular events and mortality in CHF, but the benefit of the use of IGF-1 as prognostic marker in CHF is still unresolved. Stimulation of IGF-1 receptors by the hormone can occur in response to the plasma circulating IGF-1 or to the local paracrine/autocrine production. Cardiomyocytes are able to produce IGF-1 mRNA and experimental conditions of heart hypertrophy are associated with an increase in such production, suggesting that modulation in local IGF-1 production might be an adaptive response to the need of local growth. However, no data are available on the handling of IGF-1 by the human heart in vivo in healthy subjects or in patients with CHF. Thus, aim of the current study was to clarify whether human heart in vivo is an organ that generates or rather extracts IGF-1 and whether in patients with CHF there was a change in IGF-1 handling by the heart. For this purpose, we studied the difference in IGF-1 concentrations between aorta and coronary sinus in patients with or without CHF. In addition, we also evaluated inflammatory cytokine plasma glucose concentrations and their transcoronary concentration gradients (TCG).