Expression of the granulocyte macrophage-colony stimulating factor receptor (GM-CSFR) on human myocardiocytes from end-stage heart failure patients

In remodeling ventricles, the progression of heart failure is associated with structural changes involving the extra-cellular matrix (ECM) and the cytoskeletal filament of myocardiocytes, associated with fibrosis, cellular damage and death, which lead to alterations in heart geometry, size and mechanical properties. Recently several observations have demonstrated the role of some cytokines and haemopoietic growth factors in the damage and regeneration mechanisms of cardiac tissue during acute myocardial infarction. After heart damage, the development of scarred tissue has been considered as the only reaction, since myocytes are thought to be terminally differentiated cells and thus unable to proliferate. On the contrary, recent studies in animal models and adult human hearts have shown that myocytes can proliferate before reaching their final size and that their proliferation may be stimulated and modulated by several factors. Against this background, we have investigated the expression of the receptor for GM-CSF, an haemopoietic growth factor, in healthy and end-stage human cardiac tissues, to clarify the possible role of GM-CSF and its receptor in the regenerative process of cardiac tissue in chronic cardiomyopathy. We have studied GM-CSFR expression on human cardiac tissue from explanted hearts of chronic patients with heart failure (ischemic and dilatative cardiomyopathy) and on cardiac biopsies from normal human hearts, by immunohistochemistry, cellular and molecular biology assays. Our results demonstrated the presence of GM-CSFRb in cardiac tissue; in particular GM-CSFRb positive cells were a constant finding in pathological cardiac tissues and significantly increased as compared to normal control tissues. At the moment we can only hypothesize that GM-CSF, like other growth factors, plays a role in apoptotic and/or ECM deposition processes as well as in the cytoskeleton modification in myocardium.