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 journalArticle

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

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Lymphatic Vessels
Apolipoproteins E
Hypercholesterolemia
Lipids
Dendritic Cells
Lymphatic Abnormalities
Lymphoid Tissue
Hyaluronic Acid
Dyslipidemias
Smooth Muscle Myocytes
Cell Movement
Drainage
Research

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Hwee, Y. L., Rutkowski, J. M., Helft, J., Reddy, S. T., Swartz, M. A., Randolph, G. J., & Angeli, V. (2009). Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. American Journal of Pathology, 175(3), 1328-1337. https://doi.org/10.2353/ajpath.2009.080963

Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. / Hwee, Ying Lim; Rutkowski, Joseph M.; Helft, Julie; Reddy, Sai T.; Swartz, Melody A.; Randolph, Gwendalyn J.; Angeli, Véronique.

In: American Journal of Pathology, Vol. 175, No. 3, 09.2009, p. 1328-1337.

Research output: Contribution to journalArticle

Hwee, YL, Rutkowski, JM, Helft, J, Reddy, ST, Swartz, MA, Randolph, GJ & Angeli, V 2009, 'Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration', American Journal of Pathology, vol. 175, no. 3, pp. 1328-1337. https://doi.org/10.2353/ajpath.2009.080963
Hwee YL, Rutkowski JM, Helft J, Reddy ST, Swartz MA, Randolph GJ et al. Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. American Journal of Pathology. 2009 Sep;175(3):1328-1337. https://doi.org/10.2353/ajpath.2009.080963
Hwee, Ying Lim ; Rutkowski, Joseph M. ; Helft, Julie ; Reddy, Sai T. ; Swartz, Melody A. ; Randolph, Gwendalyn J. ; Angeli, Véronique. / Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. In: American Journal of Pathology. 2009 ; Vol. 175, No. 3. pp. 1328-1337.
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