RT Journal Article
T1 Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar
A1 Ruiz-Villalba, Adrián
A1 Simon, Ana María
A1 Pogontke, Cristina
A1 Castillo, Maria I
A1 Abizanda, Gloria
A1 Pelacho, Beatriz
A1 Sanchez-Dominguez, Rebeca
A1 Segovia, Jose C
A1 Prósper, Felipe
A1 Pérez-Pomares, José María
K1 Cardiología pediátrica
AB 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.
YR 2015
FD 2015-05
LK https://hdl.handle.net/10630/33665
UL https://hdl.handle.net/10630/33665
LA eng
NO 1. Instituto de Salud Carlos III: ISCIII PI13/02144, CP09/00333, RD12/0019-0023, RD12/0019-0032, RD12/0019-00222. MINECO: BFU2012-357993. Junta de Andalucía: CTS-75644. EU FP7-Marie Curie-ITN actions PITN-GA-2011-289600
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 13 abr 2026