title: Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration.
abstract: Lymphatic vessels are essential for lipid absorption and transport. Despite increasing numbers of observations linking lymphatic vessels and lipids, little research has been devoted to address how dysregulation of lipid balance in the blood, ie, dyslipidemia, may affect the functional biology of lymphatic vessels. Here, we show that hypercholesterolemia occurring in apolipoprotein E-deficient (apoE(-/-)) mice is associated with tissue swelling, lymphatic leakiness, and decreased lymphatic transport of fluid and dendritic cells from tissue. Lymphatic dysfunction results in part from profound structural abnormalities in the lymphatic vasculature: namely, initial lymphatic vessels were greatly enlarged, and collecting vessels developed notably decreased smooth muscle cell coverage and changes in the distribution of lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1). Our results provide evidence that hypercholesterolemia in adult apoE(-/-) mice is associated with a degeneration of lymphatic vessels that leads to decreased lymphatic drainage and provides an explanation for why dendritic cell migration and, thus, immune priming, are compromised in hypercholesterolemic mice.
authors.affiliation: Department of Microbiology, Immunology Programme, Yoon Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore.
authors.forename: Hwee Ying
authors.initials: HY
authors.lastname: Lim
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rutkowski
authors.forename: Julie
authors.initials: J
authors.lastname: Helft
authors.forename: Sai T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Véronique
authors.initials: V
authors.lastname: Angeli
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D002452:Cell Count; D002465:Cell Movement; D003713:Dendritic Cells / Q000473:pathology; D006937:Hypercholesterolemia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D042601:Lymphatic Vessels / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000473:pathology
chemical_list: D001057:Apolipoproteins E
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