RT journal article T1 Long Term Response to Circulating Angiogenic Cells, Unstimulated or Atherosclerotic Pre-Conditioned, in Critical Limb Ischemic Mice A1 Beltrán Camacho, Lucía A1 Jiménez Palomares, Margarita A1 Sánchez Gomar, Ismael A1 Rosal Vela, Antonio A1 Rojas Torres, Marta A1 Eslava Alcón, Sara A1 Alonso Piñero, José Ángel A1 González Rovira, Almudena A1 Extremera García, Mª Jesús A1 Conejero, Rosario A1 Doiz Artázcoz, Esther A1 Rodríguez Piñero, Manuel A1 Røssel Larsen, Martin A1 Durán Ruiz, María del Carmen A2 BiomedicinaBiotecnología y Salud Pública A2 Cirugía K1 Circulating angiogenic cells K1 critical limb-threatening ischemia K1 atherosclerotic secretome K1 proteomics K1 neovascularization K1 immune cells AB Critical limb ischemia (CLI), the most severe form of peripheral artery disease, results from the blockade of peripheral vessels, usually correlated to atherosclerosis. Currently, endovascular and surgical revascularization strategies cannot be applied to all patients due to related comorbidities, and even so, most patients require re-intervention or amputation within a year. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative potential, although the mechanisms of action of these cells, as well as their response to pathological conditions, remain unclear. Previously, we have shown that CACs enhance angiogenesis/arteriogenesis from the first days of administration in CLI mice. Also, the incubation ex vivo of these cells with factors secreted by atherosclerotic plaques promotes their activation and mobilization. Herein, we have evaluated the long-term effect of CACs administration in CLI mice, whether pre-stimulated or not with atherosclerotic factors. Remarkably, mice receiving CACs and moreover, pre-stimulated CACs, presented the highest blood flow recovery, lower progression of ischemic symptoms, and decrease of immune cells recruitment. In addition, many proteins potentially involved, like CD44 or matrix metalloproteinase 9 (MMP9), up-regulated in response to ischemia and decreased after CACs administration, were identified by a quantitative proteomics approach. Overall, our data suggest that pre-stimulation of CACs with atherosclerotic factors might potentiate the regenerative properties of these cells in vivo. PB MDPI SN 2227-9059 YR 2021 FD 2021-09 LK http://hdl.handle.net/10498/25840 UL http://hdl.handle.net/10498/25840 LA eng NO This study was supported by the Institute of Health Carlos III, ISCIII (PI16-00784, PI2000716), co-funded by European Regional Development Fund "A way to make Europe", and the Programa Operativo de Andalucia FEDER, Iniciativa Territorial Integrada ITI 2014-2020, Consejeria de Salud, Junta de Andalucia (PI0026-2017). DS Repositorio Institucional de la Universidad de Cádiz RD 08-nov-2026