> Detailanzeige

Robichaud, Sabrina; Rasheed, Adil; Pietrangelo, Antonietta; Kim, Anne; Boucher, Dominique; Emerton, Chrissy; Vijithakumar, Viyashini; Gharibeh, Lara; Fairman, Garrett; Mak, Esther; Nguyen, My-anh; Geoffrion, Michele; Wirka, Robert; Rayner, Katey J; Ouimet, Mireille I

Abstract 102: Autophagy Is Differentially Regulated In Leukocyte And Nonleukocyte Foam Cells During Atherosclerosis

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Abstract 102: Autophagy Is Differentially Regulated In Leukocyte And Nonleukocyte Foam Cells During Atherosclerosis
  • Beteiligte: Robichaud, Sabrina; Rasheed, Adil; Pietrangelo, Antonietta; Kim, Anne; Boucher, Dominique; Emerton, Chrissy; Vijithakumar, Viyashini; Gharibeh, Lara; Fairman, Garrett; Mak, Esther; Nguyen, My-anh; Geoffrion, Michele; Wirka, Robert; Rayner, Katey J; Ouimet, Mireille I
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2022
  • Erschienen in: Arteriosclerosis, Thrombosis, and Vascular Biology
  • Sprache: Englisch
  • DOI: 10.1161/atvb.42.suppl_1.102
  • ISSN: 1079-5642; 1524-4636
  • Schlagwörter: Cardiology and Cardiovascular Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> Atherosclerosis is characterized by a build-up of foam cells in the arterial wall, resulting from excess cholesterol uptake and accumulation of cytosolic lipid droplets (LDs). Autophagy has been shown to be atheroprotective in part by promoting the catabolism of LDs which liberates free cholesterol for efflux out of foam cells to cholesterol acceptors (ApoA-I or HDL) for removal from the body. Apart from macrophages (MΦ), vascular smooth muscle cells (VSMCs) comprise 50-70% of foam cells in the plaques. Unlike MΦ, the capacity of VSMC foam cells to metabolize cholesterol via autophagy is unknown. Here, w <jats:italic>e performed a comparative analysis of the autophagic capacity and cholesterol efflux of arterial foam cell subtypes of the atherosclerotic plaque</jats:italic> . </jats:p> <jats:p> Atherosclerosis was induced in hypercholesterolemic autophagy reporter mice (GFP-LC3 mice receiving PCSK9-AAV and fed a Western diet). Autophagic flux in aortic digests was assessed by quantifying GFP-LC3 fluorescence after <jats:italic>ex vivo</jats:italic> treatment with the autophagy inhibitor Bafilomycin A1 or vehicle. MΦ foam cells displayed functional autophagy as shown by an accumulation of GFP-LC3 upon autophagy inhibition. In contrast, VSMC foam cells did not similarly accumulate GFP-LC3 upon bafilomycin treatment, suggesting dysfunction autophagy in these cells. Additionally, immunostaining of late-stage aortic roots showed MΦ, but not VSMC, foam cells induction of the active autophagy marker pATG16L1. Cell culture studies of lipid loaded MΦ and VSMC corroborated this inability for VSMCs to initiate autophagy <jats:italic>in vivo</jats:italic> . </jats:p> <jats:p> <jats:italic>In vitro</jats:italic> , MΦ foam cells effluxed cholesterol to ApoA-I (14%) and HDL (50%), whereas VSMC foam cells minimally effluxed cholesterol to HDL (7%) but not apoA-I. However, unlike MΦ foam cells, VSMC efflux was pharmacologically induced by treatment with metformin. </jats:p> <jats:p>Our data therefore demonstrates a lack of functional autophagy in VSMC, as compared to MΦ foam cells, which impairs their ability to perform cholesterol efflux. This autophagy defect in VSMC foam cells can be increased by autophagy activation using metformin, highlighting both the importance of understanding cholesterol metabolism in all foam cell populations and a new avenue to treat atherosclerosis.</jats:p>