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

Amadio, Patrizia; Macchi, Chiara; Favero, Chiara; Zara, M; Solazzo, G.; 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

doi:10.3389/fcvm.2022.906483

Cited by 5 publications

(4 citation statements)

References 84 publications

(114 reference statements)

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“…Affective disorders (anxiety and depression) represent one of the most frequent psychiatric comorbidities, as reported by different authors [8,9], including in a previous study by our group [10]. Different factors explain the vulnerability of patients with AD to mood/anxiety disorders, including the biological alterations shared by the dermatological and psychiatric illness [11], such as over-inflammation [12,13], metabolic abnormalities [2,14], or the accumulation of advanced glycation end products in the skin [15,16]. Psychosocial factors such as discomfort and discrimination related to skin lesions can also contribute to the deterioration of patients' mental health [17].…”

Section: Introductionmentioning

confidence: 76%

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Ferrucci,

Tavecchio,

Ceresa

et al. 2024

JCM

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Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

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Section: Introductionmentioning

confidence: 76%

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Ferrucci,

Tavecchio,

Ceresa

et al. 2024

JCM

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“…Then, we compared genes obtained by the miRNA target analysis, with genes associated with atherosclerosis and inflammation downloaded from DisGeNET v 7.0. In addition, for each miRNA, we performed an enrichment analysis [ 79 ].…”

Section: Methodsmentioning

confidence: 99%

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

Greco

Rizzuto

Zara

et al. 2022

IJMS

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Vascular smooth muscle cells (VSMCs) are key participants in both early- and late-stage atherosclerosis and influence neighbouring cells possibly by means of bioactive molecules, some of which are packed into extracellular vesicles (EVs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed and secreted by VSMCs. This study aimed to unravel the role of PCSK9 on VSMCs-derived EVs in terms of content and functionality. EVs were isolated from human VSMCs overexpressing human PCSK9 (VSMCPCSK9-EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMCPCSK9-EVs caused a rise in the expression of adhesion molecules in endothelial cells and of pro-inflammatory cytokines in monocytes. These acquired an increased migratory capacity, a reduced oxidative phosphorylation and secreted proteins involved in immune response and immune effector processes. Concerning macrophages, VSMCPCSK9-EVs enhanced inflammatory milieu and uptake of oxidized low-density lipoproteins, whereas the migratory capacity was reduced. When injected into zebrafish embryos, VSMCPCSK9-EVs favoured the recruitment of macrophages toward the site of injection. The results of the present study provide evidence that PCSK9 plays an inflammatory role by means of EVs, at least by those derived from smooth muscle cells of vascular origin.

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“…According to the neurotrophic theory of depression, synaptic and neuronal changes associated with depression are caused by a deficiency of growth factors, in particular the brain-derived neurotrophic factors (BDNF), the highest abundant neurotrophin detected in the adult brain [ 93 ]. Indeed, reduction of peripheral BDNF in depressed patient and in the brain regions of rodent model of depression have been reported [ [94] , [95] , [96] ].…”

Section: Introductionmentioning

confidence: 99%

NADPH-oxidases as potential pharmacological targets for thrombosis and depression comorbidity

Amadio,

Sandrini,

Zarà

et al. 2024

Redox Biology

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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

Cited by 5 publications

References 84 publications

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

PCSK9 Confers Inflammatory Properties to Extracellular Vesicles Released by Vascular Smooth Muscle Cells

NADPH-oxidases as potential pharmacological targets for thrombosis and depression comorbidity

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