2026-05-28T19:13:40Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/336652026-02-03T11:13:37Zcom_10630_2254col_10630_37953

Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar Ruiz-Villalba, Adrián Simon, Ana María Pogontke, Cristina Castillo, Maria I Abizanda, Gloria Pelacho, Beatriz Sanchez-Dominguez, Rebeca Segovia, Jose C Prósper, Felipe Pérez-Pomares, José María Cardiología pediátrica Background: Although efforts continue to find new therapies to regenerate infarcted heart tissue, knowledge of the cellular and molecular mechanisms involved remains poor. Objectives: This study sought to identify the origin of cardiac fibroblasts (CFs) in the infarcted heart to better understand the pathophysiology of ventricular remodeling following myocardial infarction (MI). Methods: Permanent genetic tracing of epicardium-derived cell (EPDC) and bone marrow-derived blood cell (BMC) lineages was established using Cre/LoxP technology. In vivo gene and protein expression studies, as well as in vitro cell culture assays, were developed to characterize EPDC and BMC interaction and properties. Results: EPDCs, which colonize the cardiac interstitium during embryogenesis, massively differentiate into CFs after MI. This response is disease-specific, because angiotensin II-induced pressure overload does not trigger significant EPDC fibroblastic differentiation. The expansion of epicardial-derived CFs follows BMC infiltration into the infarct site; the number of EPDCs equals that of BMCs 1 week post-infarction. BMC-EPDC interaction leads to cell polarization, packing, massive collagen deposition, and scar formation. Moreover, epicardium-derived CFs display stromal properties with respect to BMCs, contributing to the sustained recruitment of circulating cells to the damaged zone and the cardiac persistence of hematopoietic progenitors/stem cells after MI. Conclusions: EPDCs, but not BMCs, are the main origin of CFs in the ischemic heart. Adult resident EPDC contribution to the CF compartment is time- and disease-dependent. Our findings are relevant to the understanding of post-MI ventricular remodeling and may contribute to the development of new therapies to treat this disease. 2024-09-27T10:26:19Z 2024-09-27T10:26:19Z 2024-09-27T10:26:19Z 2015-05 journal article https://hdl.handle.net/10630/33665 10.1016/j.jacc.2015.03.520 eng open access