6533b85afe1ef96bd12b8b3e

RESEARCH PRODUCT

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

Maria Francesca GrecoAlessandra Stefania RizzutoMarta ZaràMarco CaforaChiara FaveroGiulia SolazzoIlaria GiustiMaria Pia AdorniFrancesca ZimettiVincenza DoloCristina BanfiNicola FerriCesare R. SirtoriAlberto CorsiniSilvia Stella BarbieriAnna PistocchiValentina BollatiChiara MacchiMassimiliano Ruscica

subject

Myocytes Smooth MusclePCSK9; atherosclerosis; extracellular vesicles; inflammation; vascular smooth muscle cellsPCSK9; atherosclerosis; extracellular vesicles; inflammation; vascular smooth muscle cells.Muscle Smooth VascularCatalysisPCSK9Inorganic ChemistryExtracellular VesiclesSettore BIO/13 - Biologia ApplicataSettore MED/44 - Medicina del Lavorovascular smooth muscle cellsAnimalsHumansPhysical and Theoretical ChemistryMolecular BiologyZebrafishSpectroscopySettore MED/04 - Patologia GeneraleOrganic ChemistryEndothelial CellsGeneral MedicineComputer Science Applicationsinflammationextracellular vesicles; PCSK9; atherosclerosis; inflammation; vascular smooth muscle cellsSettore BIO/14 - FarmacologiaatherosclerosisProprotein Convertase 9

description

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.

yearjournalcountryeditionlanguage
2022-10-28International Journal of Molecular Sciences
https://doi.org/10.3390/ijms232113065