RT Journal Article T1 Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo A1 Eslava-Alcon, Sara A1 Extremera-García, M. Jesús A1 Sanchez-Gomar, Ismael A1 Beltrán-Camacho, Lucía A1 Rosal-Vela, Antonio A1 Muñoz, Javier A1 Ibarz, Nuria A1 Alonso-Piñero, Jose Angel A1 Rojas-Torres, Marta A1 Jiménez-Palomares, Margarita A1 González-Rovira, Almudena A1 Conejero, Rosario A1 Doiz, Esther A1 Rodriguez-Piñero, Manuel A1 Moreno-Luna, Rafael A1 Durán-Ruiz, M. Carmen K1 Circulating angiogenic cells K1 Endothelial colony forming cells K1 Paracrine role K1 Secretome K1 Atherosclerotic factors K1 Angiogenesis K1 Proteomics K1 Células K1 Secretoma K1 Aterosclerosis K1 Inhibidores de la angiogénesis K1 Proteómica K1 Células progenitoras endoteliales AB In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment. PB MDPI YR 2020 FD 2020-07-24 LK http://hdl.handle.net/10668/3799 UL http://hdl.handle.net/10668/3799 LA en NO Eslava-Alcon S, Extremera-García MJ, Sanchez-Gomar I, Beltrán-Camacho L, Rosal-Vela A, Muñoz J, et al. Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo. Int J Mol Sci. 2020 Jul 24;21(15):5256 DS RISalud RD Apr 30, 2025