Brain-Derived Neurotrophic Factor and Extracellular Vesicle-Derived miRNAs in an Italian Cohort of Individuals With Obesity: A Key to Explain the Link Between Depression and Atherothrombosis

Patrizia Amadio, Chiara Macchi, Chiara Favero, Marta Zarà, Giulia Solazzo, Laura Dioni, Leonardo Sandrini, Luisella Vigna, Maria Francesca Greco, Massimiliano Buoli, Cesare R. Sirtori, Angela Cecilia Pesatori, Alessandro Ieraci, Massimiliano Ruscica, Silvia Stella Barbieri, Valentina Bollati

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Obesity and depression are intertwined diseases often associated with an increased risk of cardiovascular (CV) complications. Brain-Derived Neurotrophic Factor (BDNF), altered in the brain both of subjects with depression and obesity, provides a potential link between depression and thrombosis. Since the relationship among peripheral BDNF, depression and obesity is not well-defined, the aim of the present report has been to address this issue taking advantage of the contribution played by extracellular vesicle (EV)-derived miRNAs. Research Process: Associations among circulating BDNF, depression and EV-derived miRNAs related to atherothrombosis have been evaluated in a large Italian cohort of obese individuals (n = 743), characterized by the Beck Depression Inventory (BDI-II) score. Results: BDI-II was negatively associated with BDNF levels without a significant impact of the rs6265 BDNF polymorphism; this association was modified by raised levels of IFN-γ. BDNF levels were linked to an increase of 80 EV-derived miRNAs and a decrease of 59 miRNAs related to atherosclerosis and thrombosis. Network analysis identified at least 18 genes targeted by these miRNAs, 7 of which involved in depression and CV risk. The observation of a possible link among BDNF, depression, and miRNAs related to atherothrombosis and depression in obesity is novel and may lead to a wider use of BDNF as a CV risk biomarker in this specific subject group.

Original languageEnglish
Article number906483
JournalFrontiers in Cardiovascular Medicine
Volume9
DOIs
Publication statusPublished - Jul 13 2022

Keywords

  • atherothrombosis
  • BDNF
  • cardiovascular disease
  • depression
  • EV-miRNA
  • obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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