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

Autor: Greco MF; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy., Rizzuto AS; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy., Zarà M; Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 20133 Milan, Italy., Cafora M; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133 Milan, Italy., Favero C; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133 Milan, Italy., Solazzo G; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133 Milan, Italy., Giusti I; Department of Life, Health and Environmental Sciences, Università degli Studi dell'Aquila, 67100 L'Aquila, Italy., Adorni MP; Unit of Neuroscience, Department of Medicine and Surgery, Università degli Studi di Parma, 43124 Parma, Italy., Zimetti F; Department of Food and Drug, Università degli Studi di Parma, 43124 Parma, Italy., Dolo V; Department of Life, Health and Environmental Sciences, Università degli Studi dell'Aquila, 67100 L'Aquila, Italy., Banfi C; Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 20133 Milan, Italy., Ferri N; Department of Medicine, Università degli Studi di Padova, 35100 Padua, Italy., Sirtori CR; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy., Corsini A; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy., Barbieri SS; Centro Cardiologico Monzino, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 20133 Milan, Italy., Pistocchi A; Department of Medical Biotechnology and Translational, Università degli Studi di Milano, L.I.T.A., 20133 Milan, Italy., Bollati V; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133 Milan, Italy., Macchi C; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy., Ruscica M; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Oct 28; Vol. 23 (21). Date of Electronic Publication: 2022 Oct 28.
DOI: 10.3390/ijms232113065
Abstrakt: 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 (VSMC PCSK9 -EVs) and tested on endothelial cells, monocytes, macrophages and in a model of zebrafish embryos. Compared to EVs released from wild-type VSMCs, VSMC PCSK9 -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, VSMC PCSK9 -EVs enhanced inflammatory milieu and uptake of oxidized low-density lipoproteins, whereas the migratory capacity was reduced. When injected into zebrafish embryos, VSMC PCSK9 -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.
Databáze: MEDLINE
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