Buendía, PaulaMontes de Oca, AddyMadueño, Juan AntonioMerino, AnaMartín Malo, AlejandroAljama, PedroRamírez, RafaelRodríguez, MarianoCarracedo Añón, Julia María2026-02-032026-02-032014-10-23Buendía, P., De Oca, A. M., Madueño, J. A., Merino, A., Martín-Malo, A., Aljama, P., Ramírez, R., Rodríguez, M., & Carracedo, J. (2015). Endothelial microparticles mediate inflammation-induced vascular calcification. FASEB Journal, 29(1), 173-181. https://doi.org/10.1096/FJ.14-2497060892-663810.1096/fj.14-249706https://hdl.handle.net/20.500.14352/131439This work was supported by grants from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (FIS PI07/0204, PI07/0315, PI08/1038, PS09/00836, and RETICs Red Renal RD06/0016/0007), Junta de Andalucía (JA0039/2007, JA0127/2008, JA0235/2009, JA0227/2009, JA0132/2010, JA0797-2010, P08-CTS-3797, P09-CTS-5205, and P010-CTS-6337), SYSKID, and Fundación Nefrológica. J.C. was supported by a contract from Fundación de Investigaciones Biomédicas de Córdoba (Programa de Consolidación del Sistema Sanitario Público de Andalucía).Stimulation of endothelial cells (ECs) with TNF-α causes an increase in the expression of bone morphogenetic protein-2 (BMP-2) and the production of endothelial microparticles (EMPs). BMP-2 is known to produce osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that EMPs from TNF-α-stimulated endothelial cells (HUVECs) contained a significant amount of BMP-2 and were able to enhance VSMC osteogenesis and calcification. Calcium content was greater in VSMCs exposed to EMPs from TNF-α-treated HUVECs than EMPs from nontreated HUVECs (3.56 ± 0.57 vs. 1.48 ± 0.56 μg/mg protein; P < 0.05). The increase in calcification was accompanied by up-regulation of Cbfa1 (osteogenic transcription factor) and down-regulation of SM22α (VSMC lineage marker). Inhibition of BMP-2 by small interfering RNA reduced the VSMC calcification induced by EMPs from TNF-α-treated HUVECs. Similar osteogenic capability was observed in EMPs from both patients with chronic kidney disease and senescent cells, which also presented a high level of BMP-2 expression. Labeling of EMPs with CellTracker shows that EMPs are phagocytized by VSMCs under all conditions (with or without high phosphate, control, and EMPs from TNF-α-treated HUVECs). Our data suggest that EC damage results in the release of EMPs with a high content of calcium and BMP-2 that are able to induce calcification and osteogenic differentiation of VSMCs.engjournal article1530-6860https://doi.org/10.1096/fj.14-249706Digital Object Identifier (DOI)https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.14-249706restricted access611.1612.1616.1616.61576HUVECsVSMC calcificationBMP-2 osteogenic differentiationTNF-aCiencias BiomédicasSistema cardiovascularNefrología y urologíaBiología celular (Biología)2411.03 Fisiología Cardiovascular3207.04 Patología Cardiovascular3205.06 Nefrología2407 Biología Celular