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 Sanchez-Gomar, Ismael A1 Rosal-Vela, Antonio A1 Rojas-Torres, Marta A1 Eslava-Alcon, Sara A1 Alonso-Piñero, Jose Angel A1 González-Rovira, Almudena A1 Extremera-García, Mª Jesús A1 Conejero, Rosario A1 Doiz, Esther A1 Rodriguez-Piñero, Manuel A1 Larsen, Martin R A1 Duran-Ruiz, Mª Carmen K1 Circulating angiogenic cells K1 atherosclerotic secretome K1 critical limb-threatening ischemia K1 immune cells K1 neovascularization K1 proteomics 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. SN 2227-9059 YR 2021 FD 2021-09-03 LK http://hdl.handle.net/10668/18551 UL http://hdl.handle.net/10668/18551 LA en DS RISalud RD Apr 9, 2025