Publicaciones científicas
Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar
Ruiz-Villalba A(1), Simón AM(2), Pogontke C(3), Castillo MI(3), Abizanda G(2), Pelacho B(4), Sánchez-Domínguez R(5), Segovia JC(5), Prósper F(2), Pérez-Pomares JM(6).
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.
CITA DEL ARTÍCULO J Am Coll Cardiol. 2015 May 19;65(19):2057-66. doi: 10.1016/j.jacc.2015.03.520.
Nuestros autores
