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

doi:10.3389/fcvm.2022.906483

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

Front Cardiovasc Med. 2022 Jul 13:9:906483. doi: 10.3389/fcvm.2022.906483. eCollection 2022.

Authors

Patrizia Amadio¹, Chiara Macchi², Chiara Favero³, Marta Zarà¹, Giulia Solazzo³, Laura Dioni³, Leonardo Sandrini¹, Luisella Vigna⁴, Maria Francesca Greco², Massimiliano Buoli^{5

6}, Cesare R Sirtori², Angela Cecilia Pesatori^{3

4}, Alessandro Ieraci⁷, Massimiliano Ruscica², Silvia Stella Barbieri¹, Valentina Bollati³

Affiliations

¹ Brain-Heart Axis: Cellular and Molecular Mechanisms Unit, Centro Cardiologico Monzino Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
² Department of Biomolecular and Pharmacological Sciences, University of Milan, Milan, Italy.
³ EPIGET LAB, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁴ Occupational Health Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁵ Department of Neurosciences and Mental Health, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca'Granda Ospedale, Maggiore Policlinico, Milan, Italy.
⁶ Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
⁷ Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.

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.

Keywords: BDNF; EV-miRNA; atherothrombosis; cardiovascular disease; depression; obesity.