부산대학교 도서관

Myocardial infarction is a prevalent cardiovascular disease. Mechanisms of repair in the post-infarcted heart include a progressive fibrosis that severely affects cardiac performance, eventually leading to cardiac failure. Cardiac fibrosis in the context of ventricular remodeling after infarction depends on fibroblasts of the cardiac interstitium (cardiac fibroblasts), a heterogeneous population of cells which, upon interaction with other interstitial cell types, initiates a massive deposition of extracellular matrix promoting the formation of a characteristic scar. In this work we have studied the cellular components of the cardiac interstitium from the embryo to the adult. Our results show that Wilms tumor supresor (Wt1) positive epicardial-derived mesenchymal cells pioneer the formation of the cardiac interstitium along embryogenesis, followed by the peri- and post-natal incorporation of bone-marrow derived cells. Adult epicardial-derived cells robustly differentiate into cardiac fibroblasts under normal and pathologic conditions, and become the predominant fibroblast type in the post-infarction scar. Furthermore, epicardial-derived cardiac fibroblasts are shown to display stromal properties respect to bone marrow-derived cells, critically contributing to the homing and persistence of circulating cells after infarction.