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Research Paper|Volume 9, Issue 3|pp 778—789

Microvesicles from the plasma of elderly subjects and from senescent endothelial cells promote vascular calcification

Matilde Alique1,8, María Piedad Ruíz-Torres1,8, Guillermo Bodega2, María Victoria Noci3,4, Nuria Troyano1, Lourdes Bohórquez1, Carlos Luna4, Rafael Luque5, Andrés Carmona4, Julia Carracedo6,7,9, Rafael Ramírez1,9
  • 1Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
  • 2Departamento de Biomedicina y Biotecnología, Facultad de Biología, Química y Ciencias Ambientales, Universidad de Alcalá. Alcalá de Henares, Madrid, Spain
  • 3Unidad de Anestesia, Hospital Universitario Reina Sofía/Universidad de Córdoba, Córdoba, Andalucía, Spain
  • 4Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Córdoba, Andalucía, Spain
  • 5Departamento de Química Orgánica, Universidad de Córdoba, Edificio Marie Curie (C-3), Carretera Nacional IV-A, Km 396, E14014, Córdoba, Andalucía, Spain
  • 6Departamento de Fisiología Animal (II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain
  • 7Institute of Investigation, Hospital 12 de Octubre, Madrid, Spain
  • 8These authors contributed equally to this paper
  • 9These senior authors contributed equally to this paper
Received: September 7, 2016Accepted: February 26, 2017Published: March 8, 2017

Copyright: © 2017 Alique et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Vascular calcification is commonly seen in elderly people, though it can also appear in middle-aged subjects affected by premature vascular aging. The aim of this work is to test the involvement of microvesicles (MVs) produced by senescent endothelial cells (EC) and from plasma of elderly people in vascular calcification. The present work shows that MVs produced by senescent cultured ECs, plus those found in the plasma of elderly subjects, promote calcification in vascular smooth muscle cells. Only MVs from senescent ECs, and from elderly subjects' plasma, induced calcification. This ability correlated with these types of MVs' carriage of: a) increased quantities of annexins (which might act as nucleation sites for calcification), b) increased quantities of bone-morphogenic protein, and c) larger Ca contents. The MVs of senescent, cultured ECs, and those present in the plasma of elderly subjects, promote vascular calcification. The present results provide mechanistic insights into the observed increase in vascular calcification-related diseases in the elderly, and in younger patients with premature vascular aging, paving the way towards novel therapeutic strategies.