The microrna-34a-induced senescence-associated secretory phenotype (Sasp) favors vascular smooth muscle cells calcification

Estella Zuccolo, Ileana Badi, Francesco Scavello, Irene Gambuzza, Luigi Mancinelli, Federica Macrì, Calogero C. Tedesco, Fabrizio Veglia, Anna Rita Bonfigli, Fabiola Olivieri, Angela Raucci

Research output: Contribution to journalArticlepeer-review

Abstract

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a−/− mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.

Original languageEnglish
Article number4454
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number12
DOIs
Publication statusPublished - 2020

Keywords

  • IL6
  • Inflammaging
  • SASP
  • Senescence
  • Vascular calcification
  • VSMCs

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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