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Abstract
Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.
Acknowledgments
We are grateful to María José Jimenez and Rosa Moyano for technical assistance. We also thank Miss Annie Bailey for English and scientific revisions of the manuscript. This work was supported by Plan Nacional Proyectos de Investigación en Salud of Instituto de Salud Carlos III (ISCIII) Fondos Feder European Grants (PI11/01536, PI12/01489, PI014/0041 and PI14/00806); Red de Investigación Renal (REDinREN; RD12/0021/002); Comunidad de Madrid (Fibroteam; S2010/BMD-2321); Junta de Andalucía Grants JA0797-2010, P010-CTS-6337, P11-CTS-7352.
Author contributions
Rafael Ramírez, Carlos Luna, Matilde Alique, and Estefania Navalmoral conceived and designed the experiments. Estefanía Navalmoral, Maria-Victoria Noci, Lourdes Bohorquez-Magro, and Julia Carracedo performed the experiments. Carlos Luna, Matilde Alique, and Julia Carracedo analyzed the data. Rafael Ramírez and Julia Carracedo contributed reagents/materials/analysis tools. Rafael Ramírez, Julia Carracedo, and Matilde Alique wrote the paper. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.
Disclosure
Julia Carracedo is a fellow from Fundación de Investigaciones Biomédicas de Córdoba (Programa Nicolás Monardes). Carlos Luna is a fellow from Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (CTS-6337). Matilde Alique is a fellow of the program “Ayuda Postdoctoral Programa Propio” from Universidad de Alcala, Madrid, Spain. The authors report no other conflicts of interest in this work.