Amadio Patrizia, Macchi Chiara, Favero Chiara, Zarà Marta, Solazzo Giulia, Dioni Laura, Sandrini Leonardo, Vigna Luisella, Greco Maria Francesca, Buoli Massimiliano, Sirtori Cesare R, Pesatori Angela Cecilia, Ieraci Alessandro, Ruscica Massimiliano, Barbieri Silvia Stella, Bollati Valentina
Brain-Heart Axis: Cellular and Molecular Mechanisms Unit, Centro Cardiologico Monzino Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
Department of Biomolecular and Pharmacological Sciences, University of Milan, Milan, Italy.
Front Cardiovasc Med. 2022 Jul 13;9:906483. doi: 10.3389/fcvm.2022.906483. eCollection 2022.
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.
Associations among circulating BDNF, depression and EV-derived miRNAs related to atherothrombosis have been evaluated in a large Italian cohort of obese individuals ( = 743), characterized by the Beck Depression Inventory (BDI-II) score.
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.
肥胖与抑郁症是相互关联的疾病，常与心血管（CV）并发症风险增加相关。脑源性神经营养因子（BDNF）在抑郁症和肥胖症患者的大脑中均发生改变，它为抑郁症与血栓形成之间提供了潜在联系。由于外周BDNF、抑郁症和肥胖之间的关系尚不明确，本报告旨在利用细胞外囊泡（EV）衍生的微小RNA（miRNA）所起的作用来解决这一问题。
在一个以贝克抑郁量表（BDI-II）评分表征的意大利肥胖个体大样本队列（n = 743）中，评估了循环BDNF、抑郁症与动脉粥样硬化血栓形成相关的EV衍生miRNA之间的关联。
BDI-II与BDNF水平呈负相关，BDNF基因rs62,65多态性对此无显著影响；这种关联因干扰素-γ水平升高而改变。BDNF水平与80种EV衍生的与动脉粥样硬化相关的miRNA增加以及59种与血栓形成相关的miRNA减少有关。网络分析确定了这些miRNA靶向的至少18个基因，其中7个与抑郁症和心血管风险有关。肥胖症中BDNF、抑郁症以及与动脉粥样硬化血栓形成和抑郁症相关的miRNA之间可能存在联系这一观察结果是新颖的，可能会导致BDNF在这一特定受试者群体中作为心血管风险生物标志物得到更广泛的应用。
