Cardiac remodeling in postischemic end-stage human hearts: Involvement of extracellular matrix and angiogenesis-related molecules

Background: Extracellular matrix (ECM) partici- pates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis- related ECM proteins in the remodeling heart. Me- thods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α 2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as re- flected by the decreased expression of vascular endo- thelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly inter- esting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not sup- ported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.