Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration

Ying Lim Hwee, Joseph M. Rutkowski, Julie Helft, Sai T. Reddy, Melody A. Swartz, Gwendalyn J. Randolph, Véronique Angeli

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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.

Original languageEnglish
Pages (from-to)1328-1337
Number of pages10
JournalAmerican Journal of Pathology
Volume175
Issue number3
DOIs
StatePublished - Sep 2009

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