biostudies-literatureAwan SHarrington scholar innovator awardNIA NIH HHSNHLBI NIH HHSNIAHHS | NIH | National Institute of Neurological Disorders and StrokeBrightFocus FoundationBluefield Project to cure FTDFondation de FranceNINDS NIH HHSHHS | NIH | National Heart, Lung, and Blood InstituteFondation pour la Recherche MédicaleFédération Française de Cardiologie184-199https://www.ebi.ac.uk/biostudies/studies/S-EPMC8776607biostudies-literatureUnknown130(2)<h4>Background</h4>Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 (Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation.<h4>Methods</h4>We generated mice deleted for the <i>Wnt5a</i> gene in vascular smooth muscle cells. To establish whether Wnt5a also protects against cCirculation researchWnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis.PMC8776607A2016396SR37 HL06376200107044RF1 AG053391RFAG053391R01 NS093382R37HL063762FRM,PLP20170939073R01NS093382Matz RLLambert MTomasetto CAlpy FJulien-David DHerz JSchaeffer CNajib SBohm JAwan SBoucher PTerrand JMoritz CImtiaz AMartinez LOSilva-Rojas ROulad-Abdelghani MCollet XfalseWnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis.<h4>Background</h4>Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 (Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation.<h4>Methods</h4>We generated mice deleted for the <i>Wnt5a</i> gene in vascular smooth muscle cells. To establish whether Wnt5a also protects against c2022-01-01T00:00:00Z2022 Jan2025-04-22T15:33:49.538Z2025-04-06T01:23:01.946ZS-EPMC87766073488668410.1161/circresaha.121.31888110.1161/CIRCRESAHA.121.318881